We investigated the impact of GH alone, testosterone (T) alone and combined GH and T on whole body protein metabolism. 12 hypopituitary men participated in two studies. Study 1 compared the effects of GH alone with GH and T, and Study 2 the effects of T alone with GH and T. IGF-I, resting energy expenditure (REE), fat oxidation (Fox) and rates of whole body leucine appearance (Ra), oxidation (Lox) and non-oxidative leucine disposal (NOLD) were measured. In Study 1, GH treatment increased mean plasma IGF-I (p<0.001). GH did not change leucine Ra but reduced Lox (p<0.02) and increased NOLD (p<0.02). Addition of T resulted in an additional increase in IGF-I (p<0.05), reduction in Lox (p<0.002) and increase in NOLD (p<0.002). In Study 2, T alone did not alter IGF-I levels. T alone did not change leucine Ra but reduced Lox (p<0.01) and increased NOLD (p<0.01). Addition of GH further reduced Lox (p<0.05) and increased NOLD (p<0.05). In both studies, combined treatments on REE and Fox were greater than either alone. In summary, GH-induced increase of circulating IGF-I is augmented by T, which does not increase IGF-I in the absence of GH. T and GH exerted independent and additive effects on protein metabolism, Fox and REE. The anabolic effects of T are independent of circulating IGF-I.