Gnotobiotic calves were inoculated with an O5:K4:H-, urease-positive strain of Escherichia coli isolated from a 2-day-old calf with diarrhea. The calves developed elevated temperatures and passed loose mucoid feces, with or without blood. The E. coli strain was negative for heat-stable and heat-labile enterotoxins but produced high levels of Shiga-like toxin. Bacteria attached diffusely to the epithelium of the large intestine and multifocally to the epithelium of the ileum. The duodenum and jejunum were not affected. At the sites of bacterial attachment, microvilli were effaced, enterocytes were degenerate, and necrosis and exfoliation had occurred. These results confirm a previous report from England that calves may naturally contract infections similar to those caused by enteropathogenic E. coli strains pathogenic to humans or rabbits. This suggests that the calf bacterial strains, like some enteropathogenic E. coli strains, produce high levels of Shiga-like toxin and cause attachment and effacement lesions in the colonic epithelium of the infected host.