The effect of orally administered duodenal contents on preventing diarrhea in neonatal calves challenged with enteropathogenic E. coli was studied in a 3 x 2 factorial experiment with five replications. Newborn calves received either 0 or 200 ml of intestinal fluid inoculum, obtained from older milk-fed calves, 2 h after entering the isolation facility. Colostrum was consumed following inoculum administration. The uninoculated calves received colostrum 2 h after entering the isolation facility. In compliance with the 3 x 2 factorial arrangement, two-thirds of the calves received an E. coli challenge 12 or 24 h after colostrum feeding. The remaining calves were unchallenged. Raw milk was fed at the rate of 10 percent of body weight per day. All experimental calves were observed daily for physical condition, percent dry matter of feces, urine output, rectal temperature, and dietary intake. Body weight and packed cell volume (PCV) were determined every third day. Gamma globulin per 100 ml serum was determined at 24 h of age. The inoculum was assayed microbiologically for total anaerobes, anaerobic lactobacilli, total aerobes, coliforms, and aerobic lactobacilli. Twelve calves were slaughtered at seven days of age to determine microbiological populations of the duodenal tissue and digesta. During the first six days of life calves receiving the inoculum exhibited a lower incidence of diarrhea, greater daily urine output, lower PCV, and superior average daily gain as compared to the uninoculated calves. The incidence of diarrhea and its accompanying symptoms were most severe in uninoculated calves challenged at 12 h. Rectal temperature was not affected by treatment. The differences in response to the challenge between inoculated and uninoculated calves for the complete experimental period were similar, but not as great as during the first six days of life. Serum gamma globulin at 24 h of age was abnormally low in inoculated calves. Uninoculated calves possessed normal levels of serum gamma globulin. Bacterial populations of duodenal tissue and fluid of seven day old calves were not influenced by treatment. / M.S.