“In Constantinople fire devours your goods, plague takes your wife, and women your wit,” says a nineteenth-century proverb. Observers throughout the early modern era emphasized the city’s frequent and devastating epidemics, brought on by overcrowding but also by myriad problems associated with its location, climate, and economic conditions. In fact, the city’s history of epidemics began much earlier; since its establishment as the capital of the Byzantine Empire in the early fourth century, Constantinople/Istanbul has experienced numerous epidemics. Of the epidemic diseases, plague is arguably the most important, given its high levels of mortality and long-term consequences.

Plague, a bacterial disease caused by Yersinia pestis (named after the Swiss bacteriologist who first identified it in 1894), is primarily a disease of wild rodents, transferred to humans via ectoparasites such as fleas. When an infected flea bites a human, the bacterium enters the blood stream and attacks the lymph nodes, usually causing painful swellings in the groin, armpit, or neck, called buboes, a characteristic symptom of bubonic plague. Other symptoms such as fever, chills, headache, and extreme exhaustion may accompany the buboes. If the bacteria reach the lungs, pneumonic plague develops, which then can be transferred from person to person via infected droplets released into the air by coughing. If the bacteria multiply in the bloodstream, fatal septicemia may develop, causing shock, organ failure, and sudden death. Plague, either in bubonic or pneumonic form, may cause high levels of mortality (up to 60%). Today, bubonic plague can be treated successfully with antibiotics, if diagnosed early. Pneumonic plague, however, still remains a fatal condition that can kill within 24 hours, if not treated promptly.

Even though many species of mammals can host the plague, historically speaking, rats (black rats or Rattus rattus and brown rats or Rattus norvegicus) are the primary hosts for the infection, which is then transferred to humans via their fleas (Xenopsylla cheopis), among other vectors. In Istanbul, the disease typically manifested itself in its bubonic form from mid-spring to mid-summer, when climatic conditions were favorable for the reproduction of rats and their fleas. In some cases, the disease lasted in the colder months, which may suggest a prevailing pneumonic human-to-human spread.

Recent bio-archeological findings have confirmed that Yersinia pestis was the disease agent that caused three pandemics: the Justinianic plague (541–750), a second pandemic that began with the Black Death (1346–1353) and continued for several centuries, and a third pandemic that lasted from the 1860s to about 1960.

The Justinianic Plague (541 to 750)

A series of plague outbreaks began in the mid-sixth century during the reign of the Byzantine emperor Justinian the Great (r. 527–565), after whom it is named, and lasted until the mid-eighth century. This pandemic spread to a large part of the Mediterranean world, including North Africa, the Middle East, and Europe. As the capital of the Byzantine Empire and a large urban center, Constantinople did not escape the fatal consequences of these outbreaks and experienced a severe demographic decline.

Figure 1 Plague outbreaks in Constantinople during the first pandemic (541–750).

Source: Dionysios Ch. Stathakopoulos, <em>Famine and Pestilence in the Late Roman and Early Byzantine Empire: A Systematic Survey of Subsistence Crises and Epidemics</em> (Burlington, VT: Ashgate, 2004).

Where the pandemic began has been much debated, though there seems to be robust evidence for an African origin. Spreading at once to the Mediterranean Near East, the disease reached Constantinople in mid-spring 542, where it continued for four months, producing shocking effects that can be judged from the writings of contemporary authors. Perhaps the most famous account of the first pandemic was by the Byzantine historian Procopius of Caesarea, who, in his History of the Wars, left a detailed eyewitness account, describing it as a great pandemic that affected the entire world and noting its symptoms with great accuracy. Contemporary sources indicate that several thousand people of all ages died each day. Modern authors caution against taking these numbers at face value, however; most estimate a mortality rate of 20% in a population of around 400,000. Nonetheless, timely burial of the dead must have been a serious challenge; according to some accounts, this led to unconventional burial practices, like throwing corpses into large pits, towers, cisterns, ships, and the sea.

Sixteen years after the first outbreak, plague returned to Constantinople in February 558, lasted until July, and recurred periodically thereafter. Although the historical record is more abundant on the first appearance of the plague, it is nevertheless possible to establish a basic chronology of the later outbreaks. After the initial appearance of plague in 542, the capital experienced outbreaks in 558, 573–574, 599, 618–619, 698, and 747–748 (see Figure 1), for an average interval of 29.4 years. These numbers are not fully consistent with the general periodicity of the first pandemic in other areas. On the whole, the Justinianic plague had 18 waves that affected both urban and rural Europe, the Middle East, and North Africa until 750; it appeared every 11.6 years on average. This discrepancy most likely results from a lack of data rather than a real absence of plague in Constantinople, given the city’s well-established overland and maritime communication, not only with other parts of the Byzantine empire but also with areas beyond it. On the basis of what we know, however, plague recurred in Constantinople on average every 14 years or so in the sixth century, with growing intervals in the seventh and eighth centuries, which can be attributed to a combination of factors ranging from environmental and climatic circumstances that favored or impeded the survival and reproduction of rats and their fleas to the conditions of the human population and the implementation of regulations to protect the city from infections.

The city’s vulnerability to infectious disease is historically associated with its location at the intersection of overland and maritime trade and supply routes that connected the Black Sea and its Eurasian hinterland to various points in the Mediterranean world. Contemporary observers noted that disease came from the sea and spread from coastal to inland areas. Plague was typically seen in Constantinople in the “open sea” season—that is, in spring and summer, when ships brought food and other commodities, especially grain shipments from Alexandria, which brought rats along.

Late antique Byzantine society responded to such crises in a variety of ways, shaped by a range of popular and learned perceptions of epidemic diseases. It was common to see the plague as divine punishment, especially given the era’s apocalyptic frame of mind. This did not restrain people from fleeing cities experiencing a disease outbreak, because epidemics were believed to result from miasma or tainted air. Throughout the plague-affected area, flight to the countryside was the most common tactic for avoiding disease, practiced by both citizens and authorities. Flight was not an option for everyone; especially the lower classes remained in the city. With both civil and religious authorities failing to offer relief, people increasingly turned to holy men, who they believed could predict or end an epidemic, while performing charitable acts such as almsgiving and caring for the sick.

Figure 2 Plague outbreaks in Constantinople/Istanbul during the second pandemic (1347–1850).

Kostas Kostes, <em>Ston kairo tes panoles : eikones apo tis koinonies tes Hellenikes chersonesou, 14os-19os aionas</em> (Herakleio: Panepistemiakes Ekdoseis Kretes, 1995); Jean Biraben, <em>Les hommes et la peste en France et dans les pays européens et méditerranéens (Paris: Mouton, 1975); Nükhet Varlık, Plague and Empire in the Early Modern Mediterranean World: The Ottoman Experience, 1347–1600</em> (New York: Cambridge University Press, 2015).

Figure 3 Plague outbreaks in Constantinople, 1347–1453.

Source: Kostas Kostes, <em>Ston kairo tes panoles : eikones apo tis koinonies tes Hellenikes chersonesou, 14os-19os aionas</em> (Herakleio: Panepistemiakes Ekdoseis Kretes, 1995)

While the immediate consequences were dreadful, each episode of plague lasted a few months to a year, and may have left survivors in a state of relative prosperity. Economic historians have shown that, in principle, in the aftermath of an epidemic, pre-modern cities could offer better opportunities, such as increased wages. There is some evidence for increased wages after the first plague in Constantinople and an effort to bring them down to their pre-plague levels. Notwithstanding the lack of reliable population estimates for Constantinople during the first pandemic, the cumulative effects of repeated outbreaks must have been a severe population decline, especially because of the simultaneous decline in rural populations that would otherwise repopulate cities.

The Black Death and Its Successors (1346 to c. 1850)

The second pandemic broke out in 1346 and quickly spread to almost all the inhabited parts of the Afro-Eurasian world, killing between one-quarter and one-third of the population. As in the first pandemic, plague recurred regularly for many centuries afterward, causing profound social changes. The initial outbreak, known in the West as the Black Death (1346–1353), was one of the most destructive catastrophes in history.

According to historical sources, plague was brought to Constantinople in November 1347 on Genoese ships loaded with grain from Caffa in the Crimea. This first outbreak lasted for about two months in Constantinople, killing a great number of people. Eyewitness accounts describe the destruction of the plague in gruesome terms. According to the Byzantine statesman Demetrios Kydones, the dead came to outnumber the living. Another eyewitness, the Byzantine emperor John VI Kantakouzenos, thought that “no words could express the nature of the disease.”

The first outbreak was quickly followed by recurrent waves, every 7.7 years on average (see Figure 3). The city’s overland and maritime contacts, which had become much more extensive, account for the introduction of new infections. New quarantine regulations were adopted to protect the city, similar to those implemented in other Mediterranean port cities such as Ragusa and Venice. A Spanish traveler who visited Constantinople in 1438, Pero Tafur, wrote that ships had to wait for two months on the Bosphorus before entering the city, because it was feared that they would bring the plague.

Figure 4 Plague outbreaks in Istanbul, 1453–1600.

Sources: Kostas Kostes, <em>Ston kairo tes panoles : eikones apo tis koinonies tes Hellenikes chersonesou, 14os-19os aionas</em> (Herakleio: Panepistemiakes Ekdoseis Kretes, 1995); Jean Biraben, <em>Les hommes et la peste en France et dans les pays européens et méditerranéens</em> (Paris: Mouton, 1975); Nükhet Varlık, <em>Plague and Empire in the Early Modern Mediterranean World: The Ottoman Experience, 1347–1600</em> (New York: Cambridge University Press, 2015).

When the Ottomans took over the city in 1453, repeated waves of plague and warfare had depleted its population to historically low levels (around 50,000). Thus, repopulating the city was the primary concern of the Ottoman administration, which encouraged immigration and enforced a type of demographic engineering known as sürgün (compulsory resettlement). Despite all efforts, the initial population increase in the city was slow.

Moreover, a new plague broke out in 1467, killing about one-third of the city’s population. The Greek historian Kritovoulos of Imbros, who left a detailed narrative of the outbreak, noted that many fled fearfully from the city, never to return, while others confined themselves to their homes and never went out, which made the city look deserted. According to his testimony, 600 people died each day; many corpses remained unburied for days since there were no workers to remove them. However, despite the loss caused by plague, a census taken in 1477 shows that the population of Istanbul was as numerous as that of any city in the Mediterranean. Notwithstanding the frequent plagues, the sixteenth century was a time of exceptional growth for Istanbul, in which new neighborhoods were formed and old ones became more heavily populated by merchants, craftsmen, and laborers.

After 1453, the plague’s dissemination patterns and periodicity changed commensurate with the growing centralization of the expanding Ottoman territory, as well as Istanbul’s increasing importance in this process. To better understand the process, it may be helpful to study the formation of trajectories along which plague was carried to and from Istanbul, as well as the integration of these trajectories into intersecting networks of disease exchange that turned the city into the empire’s plague hub. Between 1453 and 1517, plague arrived in Istanbul mostly via overland caravan routes from the Balkans and maritime connections with European Mediterranean port cities, most prominently Venice. Plague circulated along an east–west axis in the Mediterranean world and reappeared every eight years on average.

The acquisition of Syria, Egypt, and the Muslim Holy Cities in 1516–1517 was a major turning point in Ottoman history, doubling the size and population of the empire and enhancing its position in the Mediterranean world. In the following decades, when vast areas from the Black Sea basin to the Persian Gulf were brought under Ottoman control, plague began to spread in more complex patterns. The empire strove to centralize by forging military, administrative, and economic links between the center and the newly conquered areas—links that facilitated the spread of the plague. Consequently, there were more frequent outbreaks in regions already struck by plague as well as new outbreaks in hitherto unaffected regions.

The most important outbreaks between 1517 and 1570 took place in 1520–1529, 1533–1549, and 1552–1567, with an average interval of three years. Mortality numbers also seem to have grown proportionate to the population of the city. One foreign observer, Ogier Ghiselin de Busbecq, the Habsburg ambassador to the Ottoman empire from 1554 to 1562, recorded that at the height of an epidemic, 1,000–1,200 deaths occurred daily; when the death rate dropped to 500 per day, it was interpreted to mean that the plague was receding. In the late fifteenth century, the same number would have been seen as disastrous. Nevertheless, one must keep in mind that the population of the city was up to ten times larger at the later date.

Figure 5 Plague outbreaks in Istanbul, 1600–1850.

Sources: Kostas Kostes, <em>Ston kairo tes panoles : eikones apo tis koinonies tes Hellenikes chersonesou, 14os-19os aionas</em> (Herakleio: Panepistemiakes Ekdoseis Kretes, 1995); Daniel Panzac, <em>La peste dans l’empire Ottoman, 1700–1850</em> (Leuven, Belgique: Éditions Peeters, 1985); Jean Biraben, <em>Les hommes et la peste en France et dans les pays européens et méditerranéens</em> (Paris: Mouton, 1975).

Consolidation had fully taken shape by 1570, when Istanbul was once more struck by plague that simultaneously affected vast areas in Europe, North Africa, and the Near East. This time plague continued in Istanbul almost unremittingly until the end of the century. The city had now become the principal nexus of multiple networks of disease exchange. These networks had functioned semi-autonomously before 1570; they lacked the primary locus that Istanbul would provide after that date. By 1570, Istanbul was the hub for the transmission of the disease from one part of the empire to another. This meant that a plague that broke out in any part of the empire would be swiftly transmitted to the capital and from there to the empire’s four corners. Thus, plague became almost a routine or seasonal event in most Ottoman cities, especially in Istanbul, a fact well documented in the sources. This sustained eruption peaked in 1578, 1586, and 1587, and between 1597 and 1599, but continued well after 1600 (see Figures 2 and 4). This seemingly constant presence of plague in Istanbul led some foreign observers to associate the plague with the city in the late sixteenth century, referring to the disease as le mal de Constantinople.

Plague’s persistence in Istanbul from the 1570s onward may require an explanation other than the repeated reintroduction of the disease to the city from external sources. It is possible to surmise that plague was becoming endemic among the rat population of Istanbul in the last decades of the sixteenth century, with rats sustaining the disease and passing it on to humans. Outbreaks recurred in Istanbul throughout the seventeenth century, most prominently in 1603, 1611–1613, 1620–1624, 1627, 1636–1637, 1647–1649, 1653–1656, 1659–1666, 1671–1680, 1685–1695, and from 1697 to the early eighteenth century. Eighteenth-century outbreaks were mostly minor, though major ones took place in 1713, 1719, 1728–1729, 1739–1743, 1759–1765, 1784–1786, and 1791–1792 (see Figures 2 and 5).

In the nineteenth century, major outbreaks occurred in 1812–1819 and 1835–1838. Plague gradually receded from Istanbul over the nineteenth century, which is generally credited to the implementation of quarantine measures from 1838 onward. There were no major plague outbreaks in Istanbul after this date. However, the disease continued to be reported in other parts of the empire in the early 1900s. In fact, the sustained presence of plague in the empire obscures the distinction between this pandemic and the next.

From the Mid-1800s to the Present

The third pandemic broke out in China in the mid-nineteenth century and quickly spread to much of Asia; by 1900, it had reached San Francisco. Swiftly transported by ship from port to port, this pandemic was truly global, unlike the first two endemics, which had spread primarily through the Mediterranean Sea. In contrast to some Atlantic and Pacific port cities, Istanbul did not experience a major outbreak. Although there were reported cases of plague on ships traveling to and from Istanbul in the early 1900s, the infection does not seem to have spread to the city. Quarantine policies, as well as efforts to control and exterminate rats on the ships, seem to have paid off in keeping the city free of this disease.

It was only after the introduction of antibiotics for the treatment of plague that the third pandemic was declared to be over. This occurred in 1960, though sporadic outbreaks continued in different parts of the world. According to the World Health Organization, plague remains endemic among wild rodents in some parts of the world, including parts of Central Asia, Africa, and the American southwest. Between 1989 and 2003, 38,310 cases of plague (with 2,845 deaths) were reported to the World Health Organization, which marked an increase in the incidence of human plague. Furthermore, because of its potential for use in bio-terrorism, researchers continue to study Yersinia pestis worldwide. This has recently resulted in major advances, such as the sequencing of the plague genome and establishment of its phylogenetic tree. The lasting interest in plague across disciplines continues to inform the work of plague historians.


Lester Little, “Plague Historians in Lab Coats,” Past & Present, 2011, vol. 213, no. 1, pp. 267–290;

Nükhet Varlık, “Conquest, Urbanization, and Plague Networks in the Ottoman Empire, 1453-1600,” in The Ottoman World, ed. Christine Woodhead, New York: Routledge, 2011; Joseph P. Byrne (ed.), Encyclopedia of Pestilence, Pandemics, and Plagues, Westport, Conn.: Greenwood Press, 2008;

Lester Little, Plague and the End of Antiquity : The Pandemic of 541-750, Cambridge: Cambridge University Press, 2007;

Dionysios Ch. Stathakopoulos, Famine and Pestilence in the Late Roman and Early Byzantine Empire: A Systematic Survey of Subsistence Crises and Epidemics, Burlington, VT: Ashgate, 2004;

Uli Schamiloglu, “The Rise of the Ottoman Empire: The Black Death in Medieval Anatolia and its Impact on Turkish Civilization,” in Views from the Edge : Essays in Honor of Richard W. Bulliet, New York: Columbia University Press, 2004;

Heath W. Lowry, “Pushing the Stone Uphill: The Impact of Bubonic Plague on Ottoman Urban Society in the Fifteenth and Sixteenth Centuries,” Osmanlı Araştırmaları, 2003, vol. 23, pp. 93–132;

Marie-Hélene Congourdeau, “La peste noire à Constantinople de 1348 à 1466,” Medicina nei secoli, 1999, vol. 11, no. 2, pp. 377–389;

Kostas Kostes, Ston kairo tes panoles : eikones apo tis koinonies tes Hellenikes chersonesou, 14os-19os aionas, Herakleio: Panepistemiakes Ekdoseis Kretes, 1995;

Daniel Panzac, La peste dans l’empire Ottoman, 1700-1850, Leuven, Belgique: Éditions Peeters, 1985;

Michael Dols, “The Second Plague Pandemic and Its Recurrences in the Middle East: 1347-1894,” Journal of the Economic and Social History of the Orient, 1979, vol 22, no. 2; Michael Dols, The Black Death in the Middle East, Princeton N.J.: Princeton University Press, 1977;

Jean Biraben, Les hommes et la peste en France et dans les pays européens et méditerranéens, Paris: Mouton, 1975; Halil İnalcık, “Istanbul,” The Encyclopaedia of Islam 2, electronic edition.

This article was originally written in English for History of Istanbul and published in a digitalized form in 2019; and its Turkish translation was published in 2015.