Tumor-induced alterations in insulin sensitivity and glucose metabolism were investigated by examining the effect of glucose and insulin infusions in 72-h-starved tumor-bearing (TB) rats. Following glucose infusion, the rate of glucose disappearance from the blood was similar in TB and non-tumor-bearing (NTB) rats, even though insulin concentrations were lower in TB rats. Blood lactate was increased in TB rats prior to treatment and increased immediately following glucose infusion. Insulin alone decreased blood glucose in NTB but not TB rats. When insulin was infused together with glucose, the rate of glucose disappearance increased similarly in both TB and NTB rats. The immediate increase in blood lactate seen in TB rats following glucose infusion was not apparent in the TB rats receiving insulin and glucose. TB rats infused with glucose and insulin showed a greater rise in blood alanine concentrations, compared with all other infusion regimens. While ketone body concentrations decreased in both TB and NTB rats in response to the different infusion regimens, plasma free fatty acids in TB rats were not decreased by insulin and glucose treatments. TB rats therefore not only have decreased insulin release, but adipose tissue is also less sensitive to insulin action. In vivo studies using 2-deoxy[U-14C]glucose showed that glucose uptake by the muscle and adipose tissue, but not the tumor, was significantly increased by the infusion of insulin, thereby demonstrating one of the mechanisms by which insulin may act to conserve host tissue.