Severe malnutrition (< 65% ideal body weight [IBW]) is associated with reduced insulin secretion, decreased receptor affinity, and glucose intolerance. To characterize the abnormality of mild malnutrition in terms of insulin action, both the insulin sensitivity index and insulin secretion were measured in 15 underweight and 15 normal-weight volunteers. Ten patients had localized squamous cell carcinomas of the head and neck, and 20 were normal controls. After a 10-hour overnight fast, all volunteers were studied using Bergman's modified intravenous (IV) glucose tolerance test (IVGTT). Body weight and diagnosis were compared using a 2 x 2 ANOVA. The acute insulin response to IV glucose was reduced in normal-weight and underweight cancer patients by approximately 40% to 50% (P < .05). Both groups of cancer patients had a significantly reduced rate of glucose disposal (1.25 +/- 0.29 and 1.27 +/- 0.23 %/min) compared with the healthy volunteers (1.82 +/- 0.21 and 1.81 +/- 0.24 %/min, respectively, P < .05). Glucose production (GP) was significantly increased in the underweight cancer patients versus the weight-matched volunteers (13.9 +/- 1.3 v 10.8 +/- 0.5 micromol/kg/min, P < .05). Normal-weight and underweight cancer patients had a 32% to 44% reduction in insulin sensitivity (P < .05). In contrast to the effects of cancer, underweight controls had twice the insulin sensitivity compared with normal-weight controls (P < .01). Since insulin secretion decreased in underweight controls, the increased insulin sensitivity may have been due to an increased insulin action and to factors associated with leanness.