Whole-body protein metabolism was investigated in human immunodeficiency virus (HIV) infection by primed constant infusion of L-[1-13C]leucine in 8 control and 22 HIV-infected subjects (8 stage II; 14 stage IV disease), in postabsorptive and fed states. Postabsorptive leucine flux was increased 25% in subjects with stage IV HiV infection vs that in control subjects (130 +/- 13 vs 103 +/- 10 mumol leucine.kg-1.h-1, P < 0.001); both leucine disposal by protein synthesis (111.6 +/- 12.1 vs 82.3 +/- 9.2, P < 0.001) and release by protein degradation (129.7 +/- 13.1 vs 103.4 +/- 10.2, P < 0.001) were increased. No difference in leucine balance or oxidation was found but fat oxidation was greater in subjects with HIV infection (61.1 +/- 13.0% of energy) than in control subjects (47.6 +/- 13.7% of energy, P < 0.025). Stage II subjects had intermediate values of leucine flux, not significantly different from those of control subjects. Provision of parenteral nutrition for 4 h increased leucine flux with a switch in leucine balance from net loss to net gain; this response was quantitatively similar in all groups. HIV infection increases whole-body protein turnover but does not quantitatively impair the acute anabolic response to intravenous nutrition.