Objective:To evaluate serum leptin levels in postmenopausal women who are receiving hormone replacement therapy (HRT) and postmenopausal women who are not receiving HRT with similar body mass index (BMI) to determine whether estrogens exert effects on leptin secretion.Design:Cross‐sectional, prospective study comparing serum leptin levels in premenopausal women, postmenopausal women who were not receiving HRT (group A), and postmenopausal women who were receiving HRT (group B).Results:Serum leptin levels were significantly higher in group A in comparison to group B and control women (15.82 ± 6.6 ng/ml, 8.14 ± 4.17 ng/ml, and 10.12 ± 5.48 ng/ml, respectively;p< 0.05). Total fat mass (FM) was found to be significantly higher in untreated postmenopausal women in comparison to the other two groups (22.66 ± 2.79 kg vs. 19.14 ± 3.39 kg vs. 18.98 ± 3.82 kg;p< 0.05). No significant difference was observed in weight, height, BMI, blood pressure, or glucose levels among the three groups. A linear correlation between BMI and serum leptin levels as well as between total FM and serum leptin levels was observed in all groups. No correlation was found between serum leptin levels and months from menopause and months of HRT.Conclusions:Our results show that serum leptin is increased in untreated postmenopausal women, possibly as a consequence of the increase in FM, and that HRT reduces serum leptin levels to premenopausal values. These data need further investigation by a broader longitudinal study. (Menopause2000;7:36‐41. © 2000, The North American Menopause Society.)