To determine if milk-borne insulin-like growth factor I (IGFI) is absorbed in neonatal piglets, recombinant human IGF-I was iodinated and then administered via an oral-gastric tube to newborn and 3-day-old piglets together with fluorescent isothiocyanate dextran (FITC-D70s, a macromolecular marker for assessment of gut closure). Results showed that total radioactivity and trichloroacetic acid (TCA)-precipitable radioactivity rose significantly in the plasma of both newborn and 3-day-old piglets 1 hour after oral-gastric administration of 125I-IGF-I, although the magnitude of increase was greater in newborns than in 3-day-old piglets. In contrast, significant absorption of FITC-D70s was observed only in newborn piglets but not in 3-day-old piglets. Chromatographic analysis revealed that 125I-IGF-I represented up to 20% of total plasma radioactivity in the newborns and up to 10% in the 3-day-old piglets. The 125I-IGF-I found in the plasma was mostly bound to IGF-binding proteins. These results indicate that milkborne IGF-I can be absorbed in neonatal piglets and the absorption is independent of gut closure.