A dysentery syndrome was recognized among the Institute's calves at 18 to 21 days of age. It was reproduced experimentally in gnotobiotic calves with an atypical Escherichia coli (S102-9) isolated from the affected calves. In both natural and experimental disease the calves passed copious bright red blood in the feces and developed diarrhea. Walls of the colon and rectum were thickened, and the mucosa was reddened and covered by an exudate that contained mucus and blood clots. Bacteria were seen closely adherent to the luminal surfaces of enterocytes, often in cup-shaped depressions or on cytoplasmic pedestals. Microvilli were distorted, disorientated or absent. There was exfoliation of infected enterocytes and a mild acute inflammation of the underlying lamina. In two of five calves with natural disease, the adherent bacteria did not stain by the immunoperoxidase method with antisera raised against E. coli (S102-9). This indicated that there was possibly more than one bacterial cause of the syndrome. Lesions in experimentally infected calves were indistinguishable from those produced by some E. coli which are enteropathogenic for man, rabbits, and pigs.