Diagnoses of Clostridium difficile enterocolitis and lactose intolerance were made in a neonatal foal with persistent diarrhea. It was determined that the foal had lactose intolerance on the basis of the results of a lactose tolerance test, and a diagnosis of C difficile enterocolitis was subsequently made. The foal responded to oral administration of metronidazole and lactase. Lactose intolerance is a secondary problem most commonly associated with rotavirus infection, but it can be caused by any condition affecting the small intestine. Because C difficile can affect the small intestine in foals, it was presumably the cause of the lactose intolerance in this foal with persistent diarrhea. Oral administration of lactase was not initially successful in this foal, most likely because of ongoing C difficile enterocolitis. Presumably, metronidazole was an effective treatment for C difficile enterocolitis and administration of lactase allowed for normal digestion of milk until endogenous lactose production returned. Clostridium difficile enterocolitis and lactose intolerance should be considered as differential diagnoses in neonatal foals with diarrhea, especially when the foal is bright and alert.