Cocoliztli epidemics

April to September 1576, from one valley outward

The illness was first reported in the Valley of Mexico in April 1576 and stayed largely confined around Mexico City through July.

It began moving outward in August and expanded explosively during September's rainy-season peak, reaching from central Mexico to Sonora and Guatemala within weeks.

Three or four days

Victims developed an acute syndrome of fever, jaundice, severe pain, neurological symptoms, nodules, dysentery, and bleeding. The physician Francisco Hernández, writing as an eyewitness, reported that death commonly followed within only a few days — an interval he put at three to four.

At the height of the outbreak small towns reported twenty to forty deaths a day or more, larger towns hundreds. Indigenous communities suffered extreme mortality, while contemporary reports and later analysis found Spaniards were affected much less severely, which by itself establishes neither genetic immunity nor the pathogen's origin.

Autopsies at the Royal Indian Hospital

As deaths mounted, colonial authorities directed Hernández and the barber-surgeon Alonso López de Hinojosos to examine victims and conduct autopsies at Mexico City's Royal Indian Hospital, looking for an explanation or a treatment.

The epidemic ran until its end was declared in December 1578. Deaths across 1576–1578 are estimated at 2 to 2.5 million, about half of the remaining Indigenous population — demographic estimates drawn from colonial censuses and contemporary reports rather than a count of individuals.

No pathogen has been conclusively established. Cocoliztli is a Nahuatl word meaning pest or pestilence, not the name of an identified disease.