Physiological concentrations of insulin support the in vitro growth of LB T-cell lymphoma. We could not detect similar insulin dependence in other tumor cell lines. This study reports that insulin also enhances the growth of LB cells in vivo. Mice treated with Streptozotocin (SZ) developed partial resistance to LB lymphoma growth and they survived longer (p < 0.0025) than non-diabetic mice after LB-cell inoculation. A few diabetic mice developed complete tumor resistance, manifested by total regression of the lymphoma. SZ-treated diabetic mice reconstituted with external insulin died as fast as non-diabetic mice when both were inoculated with the same number of LB cells. The SZ-treated diabetic mice did not develop resistance to the growth of BCLI B-cell leukemia, which demonstrated only a marginal proliferative response to insulin in vitro. Mice fed a low-energy diet exhibited low insulin levels and also developed resistance to lymphoma growth (50% survival 21 days vs. 15 days; p < 0.0005), supporting the concept that insulin enhances LB T-cell tumor development in mice.