[9] Ancient sources agree that the plague is likely to have appeared during the Roman siege of the Mesopotamian city of Seleucia in the winter of 165–166, during the Parthian campaign of Lucius Verus.

[11] 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 the city of Rome, 25% of those who were affected.

[15] The Antonine plague occurred during the last years of what is called the Pax Romana, the high point in the influence, territorial control, and population of the Roman Empire.

The connectivity by land and sea between the vast territories of the Roman Empire made the transfer of infectious diseases from one region to another easier and more rapid than it was in smaller, more geographically confined societies.

The view of historian Kyle Harper is that "not for the last time in history, a precocious leap forward in social development brought biological reverses".

However, the first documented case of the plague was in Smyrna (in Roman Anatolia) in 165 where the orator Aelius Aristides almost died from the disease.

[22][23] The plague endured until about 180 and another epidemic, possibly related, is reported by Dio Cassius to have struck the city of Rome in 189.

Galen briefly recorded observations and a description of the epidemic in the treatise Methodus Medendi ("Method of Treatment"), and he scattered other references to it among his voluminous writings.

He described the plague as "great" and of long duration, and mentioned fever, diarrhea, and pharyngitis as well as a skin eruption, sometimes dry and sometimes pustular, that appeared on the 9th day of the illness to be a series of symptoms.

The information that was provided by Galen does not unambiguously identify the nature of the disease, but scholars have generally preferred to diagnose it as smallpox.

The severe devastation to the European population from the two plagues may indicate that people had no previous exposure to either disease, which brought immunity to survivors.

To others, it was a minor event, documented by Galen and other writers but only slightly more deadly than other epidemics which frequently ravaged parts of the empire.

[30][31] The traditional view was expressed by Barthold Georg Niebuhr (1776–1831) who concluded that "as the reign of Marcus Aurelius forms a turning point in so many things, and above all in literature and art, I have no doubt that this crisis was brought about by that plague ...

"[32] More recently, scholar Kyle Harper said something similar: the pandemic "in any account of Rome's destiny ... merit[s] a place squarely in the forefront.

The impact of the plague forced Marcus Aurelius to recruit and train additional soldiers from among "gladiators, slaves, and bandits."