BACKGROUND: Intradialytic parenteral nutrition (IDPN), with or without exercise, has been shown to reverse the net negative whole-body and forearm muscle protein balances observed during hemodialysis. Pharmacologic doses of recombinant human growth hormone (rhGH) constitute another potential anabolic therapy in chronic hemodialysis patients. OBJECTIVE: Our goal was to examine the potential additive anabolic effects of rhGH compared with IDPN and exercise on protein and energy homeostasis. DESIGN: We studied 7 chronic hemodialysis patients in a crossover design study in which each subject participated in 2 protocols: GH (rhGH + IDPN + exercise) and no GH (IDPN + exercise). During the GH protocol, the subjects were studied after 3 daily doses of rhGH. Each subject was studied 2 h before, 4 h during, and 2 h after a hemodialysis session with the use of a primed, constant infusion of l-[1-(13)C]leucine. RESULTS: Whole-body net protein balance was -0.50 +/- 0.07 mg x kg fat-free mass(-1) x min(-1) when the patients did not receive rhGH and -0.39 +/- 0.04 mg x kg fat-free mass(-1) x min(-1) when the patients received rhGH, a 22% improvement in prehemodialysis whole-body protein homeostasis (P < 0.05). Essential amino acid muscle loss was also significantly less during the prehemodialysis period when rhGH was administered (-18 +/- 23 compared with -71 +/- 20 mmol/L; P < 0.05). The whole-body anabolic effects of rhGH observed during the prehemodialysis period persisted throughout the entire study, as evidenced by a lack of significant interaction or main effect of treatment during hemodialysis and in the posthemodialysis period. CONCLUSION: rhGH improves whole-body protein homeostasis in chronic hemodialysis patients.