Leptin is a hormone which is exclusively synthesized and secreted by adipocytes. As of yet, little is known about the complex interplay of hormones in the modulation of circulating leptin levels. To investigate the effect of growth hormone (GH) therapy on leptin, leptin serum concentrations were measured by a specific radioimmunoassay in 29 children with GH deficiency (21 boys, 8 girls; age range 3-14 years) before and after 1, 3 and 6 months of treatment with recombinant human GH. At baseline, serum leptin levels were identical to those of healthy children. Serum leptin correlated with body mass index (BMI; r=0.60, p < 0.001) and weight (r=0.48, p=0.004), but not with height, age, insulinlike growth factor 1, or insulinlike growth factor-binding protein 3, and there was no sex difference (p > 0.05). After 1 month of treatment, the leptin levels had decreased to 73+/-(SEM) 13% of individual pretreatment levels (p=0.002) and remained constant thereafter. While the correlation between leptin, BMI, and weight persisted throughout the study period, the changes in leptin concentrations during treatment were not associated with changes in BMI, weight, height, insulinlike growth factor 1, and insulinlike growth factor binding protein 3. In conclusion, this preliminary study demonstrates that serum leptin decreases during GH treatment in children with GH deficiency.