To determine the prevalence and epidemiology of enteropathogens in acute infantile diarrhea, 500 infants less than or equal to 12 months of age with diarrhea and 500 age-matched control subjects coming to a São Paulo emergency room were studied. Enteropathogens were identified in 55% of case infants and 10% of controls; enteropathogenic Escherichia coli (EPEC) of classic EPEC serotypes producing EPEC adherence factor (EAF) (26% of case infants), rotavirus (14%), Salmonella species (8%), enterotoxigenic E. coli (7%), and Shigella species (5%) were associated with diarrhea. Isolation of EAF+ classic EPEC decreased with increasing age of cases and peaked in spring, whereas rotavirus was least common in early infancy and peaked in fall and winter. Bloody stool had a 36% positive predictive value for Shigella infection, EAF+ classic EPEC were highly resistant to antimicrobial drugs. Among poor São Paulo infants, EAF+ classic EPEC equaled or exceeded rotavirus throughout the year as a cause of diarrhea bringing children to medical attention.