A cohort of 228 Mexican children less than 5 years old was followed during the enterotoxigenic Escherichia coli(ETEC) season. The incidence of ETEC diarrhea-associated and asymptomatic infections was determined, and E. coli strains isolated from stool samples were tested for heat-labile and heat-stable toxins and for expression of colonization factor antigens (CFA). Of the children, 61% had at least one ETEC infection. Children with ETEC isolated from stools were more likely to have diarrhea than were ETEC-free age-matched control children (odds ratio [OR] = 4.5; 95% confidence interval [CI] = 2.9-7.0). Strains carrying CFA/IV, CFA/I, or CFA/II were found in 23%, 18%, and 5% of ETEC infections, respectively. The risk of having diarrhea associated with a CFA-expressing versus a CFA-negative ETEC strain was the same (age-adjusted OR = 0.8; 95% CI = 0.4-1.6). These data should be considered in the development of a diarrhea vaccine containing only CFAs.