We examined peripheral insulin sensitivity in 32 patients with cancer (17 with stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The relationships between insulin resistance and tumor factors (type and stage), malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often was reduced in patients with cancer; however, the amount of glucose metabolized was not related to tumor site or stage. The decreased glucose uptake was negatively correlated with the acute-phase response but was not correlated with body-weight loss, serum albumin, or resting energy expenditure. Our results suggest that insulin resistance in cancer patients was not induced by malnutrition. Although the qualitative presence of tumor might be the major factor inducing insulin resistance, other factors such as inflammatory reactions might be involved in the development of insulin resistance.