This study was designed to:  measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and  investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances. Clinical study. University hospital. Twenty-eight obese and overweight (body mass index [BMI] >25 kg/m2) women with PCOS, 28 normal weight (BMI <25 kg/m2) women with the syndrome, and 13 obese and overweight controls (ovulatory women without clinical or biochemical hyperandrogenemia) were selected. Blood samples were collected between day 3 and day 6 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls, at 9:00 AM, after an overnight fast. Circulating levels of LH, FSH, PRL, T, Delta4-androstenedione (A), DHEAS, 17alpha-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were measured. Both normal weight women with PCOS and obese controls were less insulin resistant and had significantly higher metastin levels, compared to obese and overweight women with the syndrome. Plasma kisspeptin levels were negatively correlated with BMI, free androgen index, and indices of insulin resistance. These results indicate that metastin is negatively associated with free androgen levels. The PCOS-associated insulin resistance and consequent hyperinsulinemia probably contribute to this effect by  stimulating androgen synthesis by the polycystic ovary (PCO) and  suppressing SHBG production in the liver.