Background We examined the effect of growth hormone (GH) administration on the psychological capacity and sense of well-being in 25 patients with adult-onset GH-deficiency (GHD) Methods Very low dosages (0.5-1.0 UI day(-1) s.c. at bed-time) of recombinant human (rh)GH (n = 13; aged 50 +/- 15 years, mean +/- SD) or placebo (n = 12, 53 +/- 14 years) were given at random for a 6-month period. Quality of life was assessed by using the Italian version of the self-rating Kellner Symptom Questionnaire (KSQ) and the Hamilton Depression Scale (HDS). Results No difference in insulin-like growth, factor I (IGF-I) levels was noted between groups on entry to the study. A significant increase in IGF-I (month O 56.2 +/- 10.4 mu g L-1 vs. month 6 125.7 +/- 16.7 mu g L-1; P < 0.001) levels was noted only in the rh-GH-treated group. There was no difference in overall scores oil the KSQ between the rh-GH-treated and control groups on entry A slight, non-significant, decrease in overall scores was noted in both groups of subjects. Subsection analysis of items from the KSQ did not show significant differences in either group during the 6-month period. A significant decrease (month O 28 +/- 1 vs. month 6 25 +/- 1; P = 0.02) in the HDS score was noted in rh-GH-treated but not in placebo-treated patients. There was a significant correlation (r(s), -0.56, P = 0.05) between increase in IGF-I levels and decrease in HDS scores in rh-GH treated patients. Conclusion The data demonstrate that low rh-GH dosages significantly improve psychological profiles as rated by HDS evaluation in adult-onset patients with GHD. On the other hand, a 6-month period of treatment does not produce any significant differences in quality of life as measured by KSQ between treated patients and placebo controls.