Small intestinal development was followed in rats from 17 to 28 days of age in order to evaluate the interactions of diets, genetic preprogramming, and hormones in influencing developmental changes. Control pups, weaned naturally at 21-24 days, showed a gradual increase in body weight, intestinal length, and segmental mucosal weight, total DNA, and protein content. In contrast, pups weaned at 17 days showed an immediate increase in intestinal length, decrease in lactase, and precocious increase in sucrase and maltase. The changes in segmental mucosal weight, DNA and protein contents, however, paralleled that of controls. Pups nursed up to 25 days had a smaller body weight, shorter intestine, lighter mucosa, and lesser mucosal protein content. They showed no significant delay in the increase in sucrase and maltase together with a persistent higher level of lactase. Enterokinase and leucine aminopeptidase showed little change irrespective of the dietary modifications. Significant increases in segmental mucosal mass, DNA, and protein contents during the studied period were seen in all animals. At 19 days, early weaned pups had serum levels of corticosteroids about 3 times that of control or prolonged nursed pups. The results support the concept of an inherent biologic program as a basic control of intestinal ontogeny whereas dietary changes seem to have a modifying role and act directly, or in concert with, hormonal changes.