We have performed a series of isotopic studies in 25 adult patients with sepsis and/or trauma in order to determine the metabolic effects of recombinant human growth hormone (rHGH) administration. Twelve of the patients were receiving total parenteral nutrition, and 13 were eating a normal ward diet and were studied postabsorption. Energy and protein kinetics were quantified isotopically before rHGH administration and following a 3-day course of rHGH (20 units subcutaneously daily). In the total parenteral nutrition group the rate of net loss of protein decreased from 0.82(0.17) g kg-1 day-1 to 0.43(0.20) g kg-1 day-1 (P less than 0.02) following the administration of rHGH. The rate of appearance of leucine was not altered, suggesting that the improvement in nitrogen balance following rHGH was because of an increased rate of protein synthesis rather than reduced catabolism. In the postabsorptive group, rHGH treatment significantly increased the rate of appearance of free fatty acids (from 7.4(2.2) mumol kg-1 min-1 to 11.1(2.6) mumol kg-1 min-1, P less than 0.03) and free fatty oxidation (from 1.3(0.4) mumol kg-1 min-1 to 1.7(0.4) mumol kg-1 min-1, P less than 0.06), while the rate of leucine oxidation was reduced (from 0.44(0.05) mumol kg-1 min-1 to 0.26(0.03) mumol kg-1 min-1, P less than 0.005). Glucose appearance and oxidation remained unchanged. These results suggest that fat was being oxidized in preference to protein, which resulted in a reduction in the net rate of loss of protein of 0.3 g kg-1 day-1 (P less than 0.05). We conclude that rHGH administration is capable of significantly reducing net protein loss in septic or injured surgical patients. Recombinant HGH may be clinically useful in supporting critically ill surgical patients who require intensive nutritional support.