The Plague of Justinian (541-542) is the first known pandemic on record, and it also marks the first firmly recorded pattern of bubonic plague. This outbreak may have originated in Ethiopia or Egypt and moved northward until it reached the large city of Constantinople. The city imported massive amounts of grain to feed its citizensmostly from Egyptand grain ships may have been the original source of contagion, with the massive public granaries nurturing the rat and flea population.
The Byzantine historian Procopius records that, at its peak, the plague was killing 10,000 people in Constantinople every day. The Byzantine Emperor Justinian I ensured that new legislation was swiftly enacted so as to deal more efficiently with the glut of inheritance suits being brought as a result of the plague deaths (Moorhead, J., 1994).
Justinian had expended huge amounts of money for wars against the Vandals in the Carthage area and the Ostrogoth kingdom of Italy. He had also dedicated significant funds on the construction of great churches like the Hagia Sophia. Coming on the heels of these great expenditures, the effects this epidemic had on tax collection was disastrous. As the plague spread to port cities around the Mediterranean, it gave the struggling Goths new opportunities in their conflict with Constantinople. The plague weakened the Byzantine empire at the critical point when Justinian's armies had nearly wholly invested Italy and could have credibly reformed a Western Roman Empire. The long term effects on European and Christian history would have been enormous. As it was, the gamble Justinian took backfired and the overextended troops could not hold on. Italy was decimated by war and fragmented for centuries as the Lombard tribes invaded the north.
It should be noted that ancient historians, and Byzantine historians in particular, and Procopius above all, did not hold to modern standards of fact-checking or numerical accuracy. The actual number of deaths will always be uncertain. Modern scholars believe that plague killed up to 5,000 people per day in Constantinople at the peak of the pandemic. It ultimately killed perhaps 40 percent of the city's inhabitants. The plague went on to destroy up to a quarter of the human population of the eastern Mediterranean. A second major plague wave in 588 spread through the Mediterranean into what is now France. A maximum figure of 25 million dead for the Plague of Justinian is considered a fairly reasonable estimate.
A major pandemic would not appear again in Europe until the Black Death of the 14th century, almost 1000 years later.