Objective: The effect of insulin-like growth factor-1 (IGF-1) on energy expenditure and protein and glucose metabolism in a group of patients with thermal injury was determined. Summary Background Data: Accelerated protein catabolism is a constant feature of the hypermetabolic response to thermal injury. Insulin-like growth factor-1 has been reported to minimize protein catabolism and normalize energy expenditure in animal models of thermal injury. Methods: To determine the efficacy of IGF-1 in human burn patients, resting energy expenditure (metabolic cart), whole body protein kinetics ((N)15 Lysine), and glucose disposal (glucose tolerance test) were assessed in eight burn patients before and after a 3-day infusion of GF-1 (20 μg/kg/hr). All patients were fluid-resuscitated uneventfully and were without obvious infection at the time of study. Enteral nutrition was administered at a constant rate before and during the IGF-1 infusion. Results: Resting energy expenditure was not altered by IGF-1 (40.3 ± 2.2 vs. 39.1 ± 2.3 kcal/kg/day). However, glucose uptake was promoted, and protein oxidation decreased significantly (0.118 ± 0.029 vs. 0.087 ± 0.021 g/kg/d, p < 0.05) by IGF-1. In addition, insulin secretion, in response to a glucose challenge was blunted. Conclusions: Insulin-like growth factor-1 therapy has a beneficial effect in preserving lean body mass during severe stress conditions by minimizing the flux of amino acids toward oxidation.