Growth hormone (GH) deficiency in adults in associated with reduced muscular strength and peak oxygen uptake (peak Vo2). How these variables are influenced by long-term somatropin therapy in adults with childhood onset GH-deficiency has not been precisely defined. The effect of somatropin treatment in 20 childhood onset GH-deficient adults on muscular strength, maximal exercise capacity, and hormonal response to exercise were therefore examined in a double-blind placebo-controlled study with recombinant human GH (rhGH, 12 microg/kg/day) for 6 months, followed by 36 months of open-labeled uninterrupted therapy, after which treatment was stopped for 9 months. After 6 months of treatment, exercise capacity increased significantly, as assessed by time to exhaustion [mean change (95% CI) 0.8 (0.2, 1.4) min, P<0.05], total (accumulated) work [11.6 (0.8, 22.4) kJ, P<0.05] and peak Vo2 [2.6 (0.3, 4.9) ml/kg/min, P<0.01], whereas no significant changes were observed during placebo. This effect on exercise capacity remained unchanged during long-term somatropin treatment, mainly due to increased capacity among patients with isolated GH deficiency. Nine months after stopping treatment, peak Vo2 decreased by 11% from 32.8+/-2.5 to 29.1+/-2.1 ml/kg/min (P<0.05). Maximal muscular handgrip strength was not affected by treatment. Long-term GH therapy resulted in decreased respiratory exchange value (R value) at rest and during exercise (P<0.001), suggesting a metabolic role with increased fat combustion. Resting and submaximal noradrenaline levels decreased during somatropin treatment (P<0.05), while no effect was observed for other exercise-induced hormonal responses, including adrenaline, insulin, prolactin, renin, and ACTH. We conclude that somatropin therapy to childhood onset GH deficient adults has a favourable effect on exercise capacity and may have a potentially beneficial effect on plasma catecholamines.