Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n = 30; mean ages, 35.4 +/- 8.3 years) and postmenopausal women (n = 45; mean ages, 49.5 +/- 4.7 years) were randomly selected. Women were classified as obese (BMI > 27 kg/m(2)) and as non-obese (BMI > 27 kg/m(2)). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60 +/- 5.0; 3.67 +/- 2.44 ng/ml, respectively, P < 0.001). Obese premenopausal women (n = 15) had significantly higher plasma leptin levels (24. 60 +/- 7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n = 15; 12.50 +/- 4. 63 ng/ml) (P < 0.001). Although there was no significant difference in the plasma leptin levels between obese (n = 25) and non-obese (n = 20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P < 0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05 +/- 10.53; 14.78 +/- 6.76 ng/ml, respectively, P < 0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.