We measured the effect of human growth hormone (hGH) on urea synthesis, nitrogen retention, and glucose turnover in ten euthyroid growth hormone (GH)-deficient children before and after seven daily injections of 0.1 U/kg hGH. The patients were fed a weight-maintaining diet with 9% of energy derived from protein. Following an overnight fast, urea synthesis and glucose turnover were determined using a primed constant infusion of [ 15N 2] urea and a constant infusion of [6,6- 2H 2] glucose. Human growth hormone produced a decrease in urea nitrogen synthesis from 6.8 ± 0.5 to 4.2 ± 0.4 mg/kg · h; ( P < .01), while plasma urea nitrogen decreased from 13.1 ± 0.8 to 7.4 ± 0.8 mg/dL; ( P < .01). The decrease in urea synthesis was reflected in a corresponding decrease in urine urea nitrogen excretion (−2.8 mg/kg · h). There was a significant correlation between plasma urea nitrogen and urea synthesis rate both before ( r = 0.85, P < .01) and after ( r = 0.79, P < .01) hGH treatment. In response to hGH, there was a rise in both plasma glucose (81.4 ± 2.2 v 89.8 ± 2.3 mg/dL; P < .05) and insulin (5.7 ± 0.8 v 13.1 ± 3.0 μU/mL; P < .05), however, glucose turnover remained unchanged (4.7 ± 0.3 v 4.6 ± 0.6 mg/kg · min). After seven days of growth hormone treatment, the patients were placed on 0.1 U/kg of hGH three times a week for 6 months, and their growth rate was calculated. There was no correlation between the 6-month growth rate and the change in urea synthesis during the seven-day treatment period. We conclude that in GH-deficient children given hGH 1) the increase in nitrogen retention is accompanied by a decrease in plasma urea nitrogen and is due to decreased urea synthesis; 2) on a fixed protein diet, plasma urea nitrogen is correlated with the urea synthesis rate; and 3) fasting glucose turnover is not changed despite a rise in plasma glucose and insulin.