To determine the frequency with which acquired monosaccharide intolerance (AMI) occurs in infants less than 3 months of age, we performed a prospective descriptive study of infants admitted to the hospital for diarrhea. We searched for differences between the characteristics and causes of AMI in these infants and those of a cohort of similar-aged infants admitted with acute diarrhea (AD). Five hundred fifty-five infants less than 3 months of age admitted with diarrhea were enrolled. Nine percent of those infants had AMI, 40% had other forms of chronic diarrhea, and 51% had AD. The mean age at hospital admission was 32 days for the infants with AMI and 44 days for the infants with AD. The mean weight loss of AMI infants was 0.3 g/day since birth, and the mean weight gain was 14.3 g/day for AD infants. The mean dehydration by difference in weights at admission and 48 h postadmission was 5% for AMI and 3% for AD infants. Bacterial and viral causes of the diarrhea were similar. At admission to the hospital, infants in whom AMI subsequently developed were younger, more malnourished, had more prolonged diarrhea, and were more dehydrated than the AD infants. Malnutrition stands out as a significant antecedent factor that contributes to the development of AMI.