Recombinant human methionyl growth hormone (Protropin) (Genetech, Inc., San Francisco, CA) administered to normal volunteers receiving hypocaloric parenteral nutrition minimized weight loss and induced positive nitrogen balance. To evaluate whether growth hormone (GH) can promote anabolism in surgical patients, 11 stable malnourished individuals were studied. In the initial trial, subjects received a constant parenteral infusion of a hypocaloric diet that provided approximately 1100 kcal/24 hr and 1.3 g protein/kg/24 hr for at least 2 weeks. During 1 week, GH 10 mg was given subcutaneously daily, whereas the other week served as the control. Daily balance studies demonstrated that administration of GH resulted in significant retention of nitrogen (+3.4 g/24 h) and phosphorus (+218 mg/24 h), despite provision of only 60% of caloric requirements. With GH, serum blood urea nitrogen (BUN) and potassium fell, whereas glucose and insulin tended to rise, and levels of insulin-like growth factor 1 increased three to fourfold. Weight gain occurred with GH and was associated with positive mineral and water balance. Six patients received GH (10 mg subcutaneously daily) for 13-25 consecutive days after an initial control week. Significant nitrogen and phosphorus retention occurred over the entire period of GH administration, and no significant side effects were observed. In these depleted patients, GH caused significant and sustained nitrogen retention over a wide range of nutritional support. GH appears to enhance the efficacy of parenteral nutrition in stable individuals requiring repletion of body protein.