Neonates are vulnerable to infections because of their immature immunity. IGF-I has been reported to have profound positive effects on immune function. In this study, we investigated the effects of IGF-I on neonatal immunity. The production of IL-2, IL-4, and interferon-gamma in phytohemagglutinin (PHA)-stimulated neonatal mononuclear cells (MNC) was significantly decreased when compared with that of adults. IGF-I alone induced a high level of IL-6 mRNA expression and protein production in neonatal MNC. IGF-I significantly increased mRNA expression and protein production of both IL-6 and interferon-y but had no influence on that of IL-2 and IL-4 in PHA-stimulated neonatal MNC. Moreover, it increased neonatal interferon-gamma production in PHA-stimulated MNC to a level similar to that of adults. IGF-I could further enhance the mRNA expression of lymphocyte-activation gene 3, which is associated with interferon-gamma production and differentiation of T-helper 1 lymphocytes, in PHA-stimulated neonatal MNC. These results suggest IGF-I could promote maturation of neonatal T cells, and its potential use to enhance neonatal immunity deserves further study.