To determine if insulin-like growth factor-I (IGF-I) or multiplication stimulating activity (MSA, rat IGF-II) might directly influence small intestinal epithelium, we studied the distribution of IGF binding sites during development of the rat intestine. Cell membranes from suckling rat mucosa bound 2-6 times as much 125I-IGF-I and 3-5 times as much 125I-MSA as did adult membranes. Isolated villus cells from suckling and adult rats specifically bound both IGFs. IGF-I binding tended to remain high during suckling, whereas MSA binding fell progressively from the early suckling period. Competitive displacement studies with insulin, IGF-I and MSA demonstrated the presence of type-I and type-II IGF receptors. In vitro autoradiography of 125I-IGF-I binding sites in adult and suckling rat jejunum showed highest binding in the submucosa with extensions up into the lamina propria. Immunocytochemical localization of type-II receptors showed highest density in villus epithelium and vessel walls. Administration of MSA by oral and IGF-I by oral and parenteral routes (1 microgram/day for 6 days) to suckling rats stimulated jejunal brush border enzymes, but not intestinal growth. Developmental changes in receptor density and effects on brush border enzymes suggest a specific role for IGFs in post-natal development of the rat intestine.