OBJECTIVE: To investigate the effects of growth hormone (GH) de®ciency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH de®cient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH de®ciency showed signi®cantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid pro®le was particularly evident in women. Signi®cantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23.5 AE 11.8 ngaml vs 11.7 AE 6.9 ngaml, P 0.01). This difference remained signi®cant even when leptin values were expressed in relation to fat mass percentage (0.79 AE 0.40 vs 0.42 AE 0.17 ngaml%, P`0.05) and fat mass kg (1.32 AE 0.81 vs 0.66 AE 0.30 ngaml kg, P`0.05). Signi®cant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole signi®cant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were signi®cantly higher in women than men in the control group, but not in the patients. No signi®cant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone de®cient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid pro®le. Leptin concentrations are increased in GH de®cient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH de®ciency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.