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This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of L-[1-13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025-0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean +/- SD: 97.8 +/- 24.9 vs 131.0 +/- 23.0 mumol.h-1 x kg-1; p < 0.001), reduced leucine incorporation into protein (80.4 +/- 20.9 vs 108.8 +/- 19.6 mumol.h-1 x kg-1; p < 0.001) and reduced leucine oxidation (17.4 +/- 4.8 vs 22.2 +/- 8.1 mumol.h-1 x kg-1; p < 0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (rho = 0.51, p < 0.05) and leucine incorporation in protein correlated positively with lean body mass (rho = 0.55, p < 0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (rho = 0.71, p < 0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)