The growth mitogenic properties of IGF-I on tissues of the gastrointestinal tract are well established; however, IGF effects on enzyme maturation are less clear. To test whether IGF-I peptide administration stimulates disaccharidase activity, we administered IGF-I or the more potent analog, long [Arg3]IGF-I, at doses ranging between 2 and 12.5 µg g-1 d-1 to suckling Wistar rat pups by either continuous s.c. infusion or by three times daily orogastric gavage. Peptides were administered for approximately 6 d starting on d 6 or 12 postpartum with six to nine rats per group. The results of the study demonstrated that systemically but not orally administered IGF-I stimulated duodenal wet tissue weight (up to 85%) and length (up to 36%). Enzyme maturation was assessed by measuring disaccharidase biochemically in tissue homogenates. Enzyme activity was also localized histocytochemically in cryostat-sectioned duodenum. After systemic infusion of IGF-I, intestinal lactase activity increased proportional to mucosal mass in both age groups. Systemic infusion of the more potent analog, long [Arg3]IGF-I, precociously induced the decline in lactase activity and accelerated the appearance of sucrase activity in the rat pups infused during the later suckling period. These findings indicate that enzyme maturation can be accelerated by systemically derived IGF-I peptides. Orogastrically IGF-I peptides, delivered at pharmacologic doses, did not affect intestinal growth or digestive enzyme maturation in suckling rat pups treated between 6 and 18 d postpartum, indicating the efficacy of IGF-I peptides may depend on the route of delivery and postnatal age of the recipient.