Data defining the isolated effect of insulin on whole body protein and glucose metabolism in cancer patients are limited. Ten normal volunteers (controls), age 55 ± 3 years (mean ± SEM); 8 cancer patients, age 61 ± 3 years, weight loss 2 ± 1% (CANWL); and 8 cancer patients, age 55 ± 2 years, weight loss 18 ± 2% (CAWL), were studied in the post-absorptive state. Whole body leucine kinetics were determined during a baseline and then a study period during which insulin was infused at 1.0 milliunits/kg/min to achieve a high physiological level of 71 ±6,83 ± 5, and 64 ± 5 microunits/ml in controls, CANWL, and CAWL, respectively. Whole body net balance equals protein synthesis minus protein breakdown. Glucose disposal (mg/kg/min) is the rate of D30 infusion at steady state. Glucose disposal of CANWL and CAWL during the study period was significantly (P < 0.05, analysis of variance) less than controls (3.91 ± 0.6 in CANWL, 3.66 ± 1.0 in CAWL, and 5.87 ± 0.6 mg/kg/min in controls), suggesting resistance to insulin with respect to carbohydrate metabolism. Hyperinsulinemia, under cuglyccmic and near basal amino acid conditions, significantly reversed the negative postabsorptive leucine net balance (P < 0.05, analysis of variance) by decreasing protein breakdown in controls as well as weight-stable and weight-losing cancer patients, suggesting that cancer patients are not resistant to the anti-catabolic effect of insulin with respect to whole body protein metabolism. © 1992, American Association for Cancer Research. All rights reserved.