A prospective study to assess whether milk IgA antibodies against Escherichia coli heat labile-toxin protect breast-fed children against labile toxin-induced gastroenteritis was carried out among infants of a marginal urban area in Guatemala. One hundred and thirty children were kept under surveillance for diarrhea by periodic home visits. Stool specimens were collected from each child routinely every 2-3 weeks and during diarrheal episodes, to study the excretion of labile toxin-producing Escherichia coli. Milk samples from the children's mothers were obtained concomitantly with the fecal specimens of the infants to be analyzed for anti-labile toxin antibodies. Twenty infections by heat-labile toxin-producing Escherichia coli as a sole agent were documented among breast-fed infants. Nine of these infections resulted in gastroenteritis, while the remaining 11 were asymptomatic. At the time of infection children who became sick were ingesting breast milk with significantly (p = 0.028) lower titers of antilabile toxin IgA than those who remained healthy. Only one of the 8 infected children receiving breast milk with high titers (greater than or equal to 256) of anti labile toxin IgA developed diarrhea, compared to 8 of the 12 subjects being fed milk with low titers (less than or equal to 64) (p = 0.025). This is the first report documenting protection by IgA antibodies in milk against labile toxin-induced gastroenteritis in infected breast-fed infants.