Many cases of intrauterine growth retardation (IUGR) are the result of placental insufficiency, suggesting that potential therapies should focus on the neonate rather than the pregnant female. We wished to determine whether IGF-I could be used therapeutically to stimulate normal rates of growth in these neonates. Eight sows received 2.3 kg/d of either a control (13% protein) or protein-restricted (0.5% protein) diet from d 63 of pregnancy to parturition. Litters were reduced to 6 pigs at 3 d of age, and IUGR neonates were fostered onto a control sow. Three pigs/ litter received an osmotic minipump containing either saline or recombinant human IGF-I, delivered at 4 microg/h from d 3 to d 10 of age. Tissue protein synthesis was measured in all pigs using a flooding dose of [3H]phenylalanine. At birth, both body weight (10%) and circulating IGF-I concentration (30%) were significantly lower in IUGR than in control newborns. The infusion of IGF-I to IUGR neonates significantly increased the circulating concentration of IGF-I, growth rate, and protein and fat accretion to control levels. The infusion of IGF-I did not alter concentrations of insulin, glucose, IGF-II, or the thyroid hormones. Our results suggest that IGF-I may be a potential therapy to restore normal growth in IUGR infants.