We examined the effect of GH supplementation on the psychological capacity and sense of well-being in 36 patients with adult-onset GH deficiency (GHD). Recombinant human GH was given in a 21-month cross-over, double blind trial, and quality of life was assessed by using three self-rating questionnaires: the Hopkins Symptom Check List (HSCL), the Nottingham Health Profile (NHP), and the Psychological General Well-Being index. In addition, at the final examination the spouses completed a short questionnaire concerning their partner. Before treatment, the patients had lowered quality of life as determined by the HSCL and NHP inventories, and a correlation between the duration of GHD and the reported symptoms was observed. Upon treatment, the HSCL score was lower (better) after placebo administration (mean +/- SD, 84 +/- 21.3) than at baseline (89 +/- 18.9; P = NS) and fell to 80.2 +/- 18.5 (P < 0.001) when active drug was given. The subscales regarding anxiety, fearfulness, and cognition were the most sensitive. It was apparent that the effect determined after GH therapy in part was due to a placebo effect. With NHP, the dimensions of energy and emotions responded most to treatment. Further, the spouses observed their partners to be improved in several aspects of mood and behavior (P < 0.05 to P < 0.0001) when active drug was given. The data thus demonstrate that GH, which is known to have multiple somatic effects, produces an improvement in the quality of life of adults with GHD.