Technical Abstract: Insulin-like growth factor-I is a polypeptide growth factor found in milk that is hypothesized to play a functional role in the growth and development of the neonate, particularly the gastrointestinal tract. Considerable evidence, based on direct tracer studies with 125I-IGF-I and measurements of circulating IGF-I concentrations in neonatal animals fed a range of IGF-I doses, indicates that the intestinal absorption of IGF-I an the possible effecting on metabolism and somatic growth are negligible. However, studies in neonatal animals indicate that oral administration of pharmacological doses of IGF-I increase small intestinal mucosal growth, whereas oral IGF-I provided within the physiological range may enhance the development of intestinal lactase. Therefore, clinical trials exploring the therapeutic use of oral IGF-I as an intervention for preterm neonates and those with compromised intestinal function seem warranted. However, milk- borne IGF-I may not be essential for the normal healthy infant, perhaps because endogenous IGF-I provides a sufficient stimulus for maintenance of gastrointestinal structure and function. Future studies should explore the significance of endogenous IGF-I and whether milk-borne IGF-I may be important under pathological conditions where the endogenous IGF-I production may be compromised.