The effect of oral epidermal growth factor (EGF) on histological and biochemical changes in epithelium in the small intestine was studied in colostrum-deprived neonatal pigs. Forty-eight pigs were infected at 4 days of age with 2 x 10(7) plaque-forming units of porcine group A rotavirus and orally fed a simulated sow-milk diet supplemented with 0.0, 0.5, or 1.0 mg/L recombinant human EGF. Sixteen noninfected pigs were fed a diet without EGF supplementation. Infected pigs developed severe diarrhea; they also consumed 25% less food and gained 60% less weight than noninfected pigs. Pigs were killed 8 days postinfection to collect samples at seven equidistant points in the small intestine. Rotavirus infection decreased villus height by 37% and reduced specific activity of lactase by 54%, of leucine aminopeptidase by 43%, and of alkaline phosphatase by 54% in the small intestine, compared with noninfected pigs. Only the supraphysiological dose of EGF (1.0 mg/L) consistently increased villus height in the proximal and mid-small intestine and lactase-specific activity in the mid-small intestine of rotavirus-infected pigs. However, this dose was only partially effective in restoring intestinal mucosal dimensions and enzyme activities. Supplemental EGF did not hasten the resolution of diarrhea. These data indicate that high physiological levels of EGF are beneficial in stimulating recovery of epithelium in the small intestine following rotavirus infection.