Concentrations of alpha-1-antitrypsin (AT) in random fecal samples from 68 infants (92.7% outpatients) with acute diarrhea and 32 healthy controls were determined. The mean +/- s.d. for AT in infants with diarrhea was 2.07 +/- 1.88 mg/g dry stool (mg/g d.s.) compared with 1.29 +/- 0.72 mg/g d.s. (p less than 0.05) in controls. Fecal AT was significantly greater than that of the controls only for diarrhea caused by Rotavirus or Salmonella. Salmonella patients also had significantly higher fecal levels of AT than patients with diarrhea caused by Campylobacter. Fifty percent of the infants with Salmonella infections excreted more than 2.73 mg/g d.s. AT, which is above the control mean + 2 s.d. Fecal excretion of AT was highest in patients with macroscopic intestinal bleeding, but it still depended more on the causative agent than on bleeding per se. This finding of increased intestinal protein loss during acute diarrhea, even in the less severe diseases, emphasizes the necessity to rapidly restart adequate nutritional intake.