Insulin-like growth factor I (IGF-I) is a growth factor for the immune system, increasing lymphocyte number and function via greater lymphocyte generation and/or survival. We investigated the effects of IGF-I on lymphocyte survival and regeneration in the thymus and spleen after dexamethasone (Dex) treatment in rats maintained with parenteral nutrition and given recombinant human IGF-I (800 micrograms/day) for 12 h, 48 h, and 5 days. IGF-I did not prevent Dex-induced apoptosis of thymocytes but reduced cell death in the spleen at 12 and 48 h. IGF-I exerted a modest protective effect (10-15% reduction in cell loss) on all splenic T and B cell subsets examined by flow cytometry. IGF-I enhanced recovery of CD4+8+ immature T cells in the thymus and decreased the proportion of CD8+ (cytotoxic/suppressor) T cells in the spleen. In rats not treated with Dex, IGF-I significantly increased total lymphocyte number and the number of CD4+8+ T cells in thymus and spleen. Our results suggest that IGF-I may alter homeostasis in the immune system by modulating lymphocyte generation and survival.