Obesity occurs in 60% of women after menopause and is characterized by an excess of adipose tissue that depends on several orexigenic (neuropeptide Y (NPY) stimulates carbohydrate ingestion, galanin stimulates fat intake) and anorectic (leptin, cholecystokinin (CCK)) factors. Both leptin and insulin can reduce hypothalamic NPY production and secretion. Behavior related to the consumption of food is probably attributed to the NPY-galanin signalling route. We investigated basal levels of serum leptin, CCK, galanin and NPY in 16 non-obese premenopausal women, in 15 obese premenopausal women (body mass index (BMI) 34.6 +/- 1.3 SD) and in ten obese postmenopausal women (BMI 34.7 +/- 1.5 SD) to determine the relationship between obesity, menopause and these neuropeptides. Obese premenopausal women had three-fold elevations of serum leptin (32.1 +/- 3.2 ng/ml) in comparison to non-obese premenopausal women (10.3 +/- 1.5 ng/ml), but similar levels to those in obese postmenopausal women (35.3 +/- 4.1 ng/ml). In all 44 patients and in both sub-groups of premenopausal and postmenopausal women, serum leptin exhibited a strong positive correlation with BMI (r = 0.8692, p < 0.0001; r = 0.8803, p = 0.0001; r = 0.8184, p = 0.0001, respectively). Serum galanin values showed a statistically significant increment in the obese postmenopausal group (51.1 +/- 8.1 pg/ml) compared to both premenopausal groups: the non-obese (34.9 +/- 5.8 pg/ml) and the obese (36.0 +/- 5.5 pg/ml). Non-obese menstruating women demonstrated NPY levels (175.0 +/- 12.8 pg/ml) significantly higher than those of obese premenopausal women (126.0 +/- 12.1 pg/ml) and obese postmenopausal women (138.1 +/- 15.4 pg/ml). CCK values showed no differences between non-obese and obese pre- and postmenopausal groups. Basal insulin values were elevated in both obese groups compared to non-obese premenopausal women. Significantly increased leptin and galanin levels in postmenopausal obese women coupled with decreased NPY levels revealed some changes in the neuropeptides regulating eating behavior, which may be the reason for the onset of postmenopausal obesity.