Technical Abstract: Previous studies with cesarean-derived, colostrum-deprived neonatal pigs have shown that oral IGF-I increases intestinal lactase activity at physiological doses, and mucosal protein and DNA mass at pharmacological doses. To establish the mechanism of these dose-dependent responses, we determined the effect of oral IGF-I on intestinal protein synthesis, lactase processing and crypt cell proliferation. One-day-old, vaginally delivered, colostrum-fed pigs were fed (1) formula (n=5), (2) formula + low IGF-I (0.5mg/L;n=6), or (3) formula + high IGF-I (12.0mg/L;n=6) for 14 d. Pigs were fed 300-350 mL/kg body weight daily. On d 15, intestinal protein synthesis and lactase processing were measured in the fed state using an intravenous multiple stable isotope infusion of 2H3-Leu, 13C1-Leu, 2H5-Phe, 13C6-Phe, and 13C9-Phe for 6 h. Cell proliferation was measured using an intraarterial injection of BrdU 2 h prior to killing. In contrast to previous studies, no effect of IGF-I was observed on intestinal weight, protein, DNA content, or lactase and sucrase activities. It is possible that (1) either the process of vaginal birth or colostrum ingestion may negate the effects of IGF-I, (2) the anabolic effects of IGF-I occur only during the early neonatal period, or (3) the increases in enzyme activity are only detectable in the postabsorptive state.