The response to dietary treatment of patients with chronic post-infectious diarrhea and lactose intolerance was prospectively studied in 29 infants less than 1 year of age. All had gastroenteritis with diarrhea which persisted for more than 3 weeks. In the hospital, diarrhea continued and lactose intolerance was documented while being fed half-strength cow's milk formula. They were given dietary treatment with one of three formulas used for treatment of diarrhea in infancy. Improvement of diarrhea was more frequently achieved with Pregestimil when given as the initial therapy than with the other two formulas. With Pregestimil nine of 10 patients improved whereas only four of nine infants fed Portagen and one of 10 patients initially treated with soy formula improved. Pregestimil was also effective in three of five patients who initially failed to improve with Portagen and in four of eight patients tried with soy formula with or without carbohydrate. Additionally, in the patients who improved, recovery was more rapidly achieved with Pregestimil than with the other two formulas. Formula failures were due to intolerance to glucose polymers in three patients, possibly to protein in seven infants, and an intolerance to all nutrients in five patients. The improvement of the diarrhea was slower in patients who had evidence of colitis in rectal biopsies regardless of the dietary treatment given, but was not correlated with other variables, i.e., etiology of diarrhea, jejunal histology, or duration of diarrhea prior to treatment. However, as a group, the patients who failed to respond to Pregestimil were younger (less than 3 months of age), had more formula changes and associated infections, and were given more antibiotics; they also had more prolonged diarrhea before treatment and more severe jejunal mucosal lesions and jejunal bacterial overgrowth. The data suggests that Pregestimil seems to be the most effective formula for the treatment of infants with chronic post-infectious diarrhea and lactose intolerance.