Plague of Athens
In the second year of the Peloponnesian War (430 BC), when an Athenian victory still seemed within reach, the city of Athens was hit by a devastating epidemic.
Because the Spartans had a much greater army, the Athenians were forced to retreat behind the city walls of Athens. From there, they hoped to keep the Spartans at bay, allowing the Athenian navy to cut off supply lines.
Thucydides described the coming of an epidemic disease which began in Ethiopia, passed through Egypt and Libya, and then came to the Greek world. The epidemic broke out in the city, which was tightly packed with people. Athens was decimated by this plague, losing a possible third of the populace. It killed many of Athens's infantry, some expert seamen and their leader, Pericles. Leaderless and weakened, the remaining Athenians fought bravely but were defeated.
Note that historians disagree on whether the plague was a critical factor in the loss of the war. However, the loss of the war may have paved the way for the success of the Macedonians and, ultimately, the Romans.
Historians have long tried to identify the disease behind the plague of Athens. It has usually been considered an example of bubonic plague, but recent examination of the reported symptoms has led some scholars to believe this disease was either measles or smallpox. Others have suggested anthrax, tramped up from the soil by the thousands of refugees from Attica hiding out in Athens. Typhus and ebola are also candidates.