Objective: The aim of this study was to evaluate the influence of menopausal status, serum estradiol and body mass index (BMI) on serum leptin concentration in a large sample of pre- and postmenopausal women. Design: 434 healthy women (mean age +/- S.D., 52.2 +/- 10.3 years) were recruited at the University of Marburg on the occasion of a routine gynecological visit. Two hundred and eighteen (50.2%) women were premenopausal (mean age, 36.5 +/- 10.4 years) and not on oral contraceptives or hormone replacement therapy (HRT) and 216 (49.8%) women were postmenopausal (mean age 61.8 +/- 8.9 years) not on HRT. To evaluate the influence of menopausal status, estradiol level and BMI on serum leptin concentrations, women were allocated to one of the four groups: (a) premenopausal women BMI <25 kg/m(2) (n = 137). (b) premenopausal women BMI >25 kg/m(2) (n = 81), (c) postmenopausal women BMI <25 kg/m(2) (n = 94) and (d) postmenopausal women BMI >25 kg/m(2) (n = 122). Results: Irrespective of the menopausal status, women with a BMI >25 kg/m(2) had significantly higher leptin concentrations in all age groups compared with women with a BMI <25 kg/m(2) (P < 0.001). The multiple linear regression analyses showed that BMI was the only statistically significant independent predictor for leptin. In comparison to postmenopausal women, premenopausal women showed a significantly lower mean age, weight, BMI and FSH concentration (P < 0.001), a higher mean height and serum estradiol (P < 0.01 and P < 0.001 respectively) but significantly lower serum leptin concentration (P < 0.01). The multiple linear regression model showed no significant influence of menopausal status or serum estradiol on serum leptin concentration, even after controlling for BMI. Conclusions: Serum leptin concentrations are significantly higher in pre- and postmenopausal obese women, compared with normal weight controls. Serum leptin concentrations are not influenced by menopausal status or serum estradiol level.