Increase in serum androgen levels results in suppression of serum leptin levels. In this study, the changes in serum leptin concentrations of children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) with respect to their hyperandrogenism were investigated. Eleven children with 21-OHD and 25 healthy control children were included in the study. Before initiation of hydrocortisone, serum leptin levels in children with CAH were lower (1.7 +/- 1.3 ng/ml) than in the control group (5.3 +/- 4.01 ng/ml) (p<0.001). After three months of treatment, serum leptin levels increased to the normal range (7.1 +/- 2.9 ng/ml). Prior to and on hydrocortisone treatment in CAH, serum leptin levels were positively correlated with cortisol (r:0.78, p:0.004 and r:0.80, p:0.003) but negatively correlated with testosterone (r:-0.62, p:0.04 and r:-0.65, p:0.002). These results suggest that serum leptin measurements may be used as an additional parameter in the follow-up of children with CAH to evaluate the efficacy of hydrocortisone treatment with respect to androgenemia.