Outbreaks of acute hepatitis occurred in Huitzililla and Telixtac, two rural villages 70 miles south of Mexico City, Mexico, in late 1986. The first outbreak began in Huitzililla in June of that year, 1 month after the start of the rainy season. A census revealed 94 icteric case subjects, for an attack rate of 5%; two women died. Attack rates were higher for persons older than 15 years (10%) than for younger persons. A case-control study showed that illness was highly associated with water-related factors. The second outbreak began in August 1986 in Telixtac. There were 129 case subjects, for an attack rate of 6%; one woman died. Epidemiologic findings were similar to those in Huitzililla, except that most disease transmission was not linked to unsafe water sources. None of 62 case subjects in Huitzililla and only 2 of 53 case subjects in Telixtac tested had serological evidence for recent infection with hepatitis A or B. Two of eight stool samples from Huitzililla and one of the eight stool samples from Telixtac were positive by immune electron microscopy for 32- to 34-nm viruslike particles similar to those seen in cases of enterically transmitted non-A, non-B hepatitis from Asia. To our knowledge, these investigations document for the first time the epidemic transmission of enterically transmitted non-A, non-B hepatitis virus in the Americas.