The effect of chronic inflammation, corticosteroid therapy, and nutritional supplementation on whole body protein metabolism and growth was determined in adolescent males with Crohn disease and growth failure. Body protein status was characterized in six patients and in five healthy, age-matched controls by nitrogen balance, whole body potassium (measured as 40K), urinary creatinine excretion, and [15N]glycine turnover studies. The patients subsequently received an intragastric nutritional supplement that increased dietary protein and energy intakes by 40% for seven months. Follow-up anthropometric measurements were obtained in both groups of adolescents. Our results demonstrated that lean body mass (40K) and muscle mass (creatinine) were significantly reduced in the patients compared to the controls, despite similar nitrogen balances between both groups. Whole body nitrogen flux, rates of protein synthesis and breakdown, and net protein retention were no different between those patients with chronic inflammation, while receiving corticosteroid therapy, and their controls. Long-term nutritional supplementation significantly improved linear and ponderal growth velocities in the patients such that growth rates were commensurate with those of the healthy controls. We conclude that chronic inflammation and corticosteroid therapy are not associated with detectable alterations in protein metabolic processes at the whole body level. Rather, dietary insufficiency appears to be primarily responsible for growth failure in adolescents with Crohn disease.