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The Antonine Plague of 165 to 180 AD, (Also known as the Plague of Galen, after Galen, the physician who described it), was an ancient pandemic brought to the Roman Empire by troops who were returning from campaigns in the Near East.

Ancient sources agree that the plague appeared first during the Roman siege of the Mesopotamian city Seleucia in the winter of 165–166. Ammianus Marcellinus reported that the plague spread to Gaul and to the legions along the Rhine. Eutropius stated that a large proportion of the empire's population died from this outbreak.

According to the contemporary Roman historian Cassius Dio, the disease broke out again nine years later in 189 AD and caused up to 2,000 deaths a day in Rome, one-quarter of those who were affected.[6] The total death count has been estimated at 5–10 million and the disease killed as much as one-third of the population in some areas and devastated the Roman army.

Scholars have suspected it to have been either smallpox or measles.

The historian William H. McNeill said that the Antonine Plague and the later Plague of Cyprian (251–c. 270) were outbreaks of two different diseases, one of smallpox and one of measles but not necessarily in that order.

The plague may have claimed the life of a Roman emperor, Lucius Verus, who died in 169 and was the co-regent of Marcus Aurelius. The two emperors had risen to the throne by virtue of being adopted by the previous emperor, Antoninus Pius, and as a result, their family name, Antoninus, has become associated with the pandemic.