OBJECTIVES:The aim of the study was to examine insulin homeostasis during growth hormone (GH) therapy, and to investigate the effect of GH treatment on insulin and leptin concentration in obese children. SUBJECTS: Nineteen obese children (8 with Prader-Willi Syndrome (PWS)) were treated with GH 0.1 IUakgaday dose for 3 months and were compared with 29 non-treated age and sex matched obese children (9 PWS) and 49 GH treated non-obese short children. Mean age of the children was 10.3 AE 1.8 (6.7 ± 13.8) y, with body mass index of 23.6 AE 10.4 (11.5 ± 47) kgam 2 . RESULTS: Leptin concentration decreased and was correlated inversely with initial leptin value (r 2 À0.374, P`0.001) and decreased body mass (r 2 0.338, P 0.001). Insulin sensitivity index was not signi®cantly changed during therapy. Leptin decrease after 3 months of GH administration was correlated inversely with the increase in ®rst phase insulin response to intravenous glucose tolerance test (IVGTT) (r 2 À0.595, P`0.001). Results of long-term follow-up of treated patients demonstrated a decrease in insulin concentration after cessation of therapy. In GH-treated subjects, the glucose increase in response to glucose load appeared to be higher than in untreated subjects. CONCLUSION: The high insulin response to glucose load seen in GH-treated subjects was appropriate to their glucose concentration and the insulin sensitivity index was unchanged relative to the pretreatment period. Increased insulin dosage in our patients did not induce an increase in leptin concentrations as had been hypothesised.