OBJECTIVE Recent data raised the possibility that high leptin levels may contribute to infertility in some women with PCOS. METHODS To assess changes in leptin levels and its relationship to some hormonal changes (insulin, testosterone, SHBG, FSH, LH, and prolactin) associated with PCOS in obese (n = 27) and nonobese (n = 18) patients when compared to obese and nonobese normal controls (n = 20). RESULTS Leptin concentration were significantly higher in PCOS than in controls, p < 0.05, with 81% sensitivity and 50% specificity. Whereas, high serum insulin levels were found in obese and nonobese women with PCOS, high serum leptin, FAI together with reduced SHBG were found in obese rather than nonobese PCOS women. Moreover, hyperleptinemia in PCOS women was not correlated to hyperinsulinemia (r = -0.13 and -0.4 in obese and nonobese PCOS women, respectively). In the patient's group correlation analysis between fasting serum leptin and different studied variables showed some correlation with body mass index (BMI) only (r = 0.413) suggesting that high leptin levels could be a characteristic of the obese PCOS. However, multiregression analysis showed that together with testosterone, leptin can successfully predict the presence or absence of PCOS. CONCLUSIONS The potential significance of leptin for the pathophysiology of PCOS will await direct studies of the effects of exogenous leptin and/or its inhibitors on the reproductive axis of women, including those with PCOS.