Malnutrition is associated with glucose intolerance. This could be related to decreased pancreatic insulin secretion and/or peripheral insulin resistance. We have used the euglycemic-hyperinsulinemic clamp and continuous indirect calorimetry to assess the disposal of an intravenous glucose load in 13 malnourished patients with benign disease (median age, 55 years; mean weight loss 21 kg +/- 8 SD). Seven normally nourished controls were also studied (median age, 62 years) and eight patients were restudied after 14 days on continuous glucose-based intravenous nutrition (IVN). With hyperinsulinemia of 90 microU/mL, malnourished patients disposed of 6.1 mg glucose/kg fat-free body (FFB).min +/- 1.7 SD and oxidized 1.9 mg/kg FFB.min +/- 1.4 SD. Controls disposed of a similar amount of glucose (6.6 mg/kg FFB.min +/- 3.5 SD) but oxidized significantly more (3.0 mg/kg FFB.min +/- 2.3 SD). After two weeks of glucose-based IVN, both glucose disposal rate (9.5 mg/kg FFB.min + 2.3 SD) and oxidation rate (3.9 mg/kg FFB min +/- 1.0 SD) increased significantly. Respiratory quotient was low in malnourished patients (.88 +/- .12), but above 1.0 in controls (1.07 +/- 0.18) and patients after IVN (1.10 +/- 0.11), showing net lipogenesis in these groups. Malnourished patients can metabolize normal amounts of glucose under conditions of hyperinsulinemia and, although carbohydrate oxidation rate is initially impaired, it becomes normal after 2 weeks of IVN.