BACKGROUND Insulin resistance has been shown to have an association with polycystic ovary syndrome (PCOS). This study was designed to evaluate the potential role of adiponectin, which is linked with insulin resistance, in the etiology of PCOS and its relationship to obesity. METHODS This case-control study consisted of 103 newly diagnosed PCOS cases and 73 female controls seen at a referral university hospital in Zanjan, Iran. Serum adiponectin, insulin, plasma fasting glucose, and lipid levels were measured. The homeostasis model assessment index was used to determine the level of insulin resistance. Women were classified as follows: Group I (normal nonlean women); group II (normal lean women); group III (nonlean women with PCOS); and group IV (lean women with PCOS) RESULTS: Adiponectin levels were decreased in women with PCOS (8.4 +/- 2.7 ng/mL vs. 13.6 +/- 5 ng/mL in the control group, P < 0.001). There was no significant difference between the adiponectin concentrations of women in group III and that in group IV (8.1 +/- 2.8 ng/mL vs. 9.2 +/- 2.6 ng/mL, respectively, P = 0.1). Adiponectin levels were significantly lower in group I compared with group II. A weak but significant negative correlation was found between adiponectin and insulin levels in all the subjects. Multiple regression analyses showed that the presence of PCOS was the only significant determinant of serum adiponectin levels. CONCLUSIONS Adiponectin levels were reduced in all the women with PCOS. There seemed to be an interaction between adiponectin and PCOS pathogenesis that was independent of body mass index.