Fifteen infants (age 3-28 wk) suffered from severe diarrhea with acute dehydration and poor growth. Persistent watery stools and suboptimal nutrition necessitated central venous alimentation with prolonged hospitalization. Repeated stool and small intestinal fluid cultures yielded the classical enteropathogenic Escherichia coli serotype 0119:B14. In all patients, biopsy of the jejunum or rectal mucosa, or both, showed moderate to severe damage, irregular atrophy of surface epithelium, and subnuclear vacuolization of crypt epithelium. Ultrastructural studies revealed bacteria adherent to mucosal cells with flattening of microvilli, loss of the cellular terminal web, and cupping of the plasma membrane around individual bacteria. Heavily colonized cells had marked intracellular damage. Assays for heat-labile, heat-stable, and vero cell toxins were negative for these Escherichia coli isolates. Oral neomycin and nutritional support resulted in clearing of Escherichia coli 0119:B14 from stool and small bowel with improvement in histologic characteristics. Damage to enterocytes and villi by adherent nontoxigenic Escherichia coli 0119:B14 results in protracted diarrhea in infants.