Human growth hormone (rhGH) increases estimates of whole-body protein synthesis, but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In addition, rhGH stimulates protein synthesis in skeletal muscle tissue. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. Using high-dose prednisone as a controlled model for protein catabolism in normal volunteers, high-dose rhGH together with prednisone prevents the protein catabolic effects of prednisone alone. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole body proteolysis, suggestive of a predominant insulin-like effect. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. Thus, the mechanism of action of rhGH on body protein metabolism remains to be elucidated. However, rhGH alone or in combination with rhIGF-I may provide a new management strategy in a variety of protein catabolic conditions in humans.