A randomized, investigator-masked trial determined the effects of oral recombinant human transforming growth factor-α (TGFα) on jejunal mucosal recovery in 75 piglets with rotavirus diarrhea. Rotavirus inoculation of artificially reared piglets induced subtotal (∼50%) villus atrophy and watery diarrhea. Dietary TGFα was associated with significant restoration of villus surface area by 4 d postinoculation (p.i.) and complete restoration by 8 d p.i., whereas saline-treated animals required 12 d for recovery. Jejuna segments from clinically recovered TGFα-treated piglets showed an increase in electrical resistance across the epithelial barrierin vitrowhich was proportional to villus height. TGFα treatment for 12 d also produced a 30–50% increase in jejunal mucosal mass (protein content and wet weight), compared with the corresponding values in salinetreated piglets and in uninfected controls. However, oral TGFα did not hasten the resolution of diarrhea, enhance the specific activities of jejunal mucosal digestive enzymes, or increase jejunal glucose-stimulated Na+absorptionin vitro.We conclude that dietary TGFα stimulates jejunal mucosal hypertrophy, improves barrier function, and enhances regrowth of villi in rotavirus enteritis; however, it does not facilitate the restoration of functional activity or mucosal digestive enzymes. Oral TGFα can facilitate intestinal epithelial recovery in diseases associated with mucosal damage.