Insulin secretion in response to iv glucose and insulin sensitivity (euglycemic hyperinsulinemic clamp) were evaluated in 49 women with polycystic ovary syndrome (PCOS) [body mass index (BMI), 17.6-37.2 kg/m2] and 42 control subjects (BMI, 18.8-38.1 kg/m2). Seven women with PCOS exhibited glucose intolerance with subnormal insulin secretion. Compared with control subjects, women with PCOS and normal glucose tolerance had an increased (36-56%) insulin increment, not explained by insulin resistance, and over the whole range of BMI. In contrast, insulin sensitivity was similar in women with PCOS and control subjects at BMI 21 kg/m2, but showed a more pronounced decline with increasing BMI in women with PCOS, who had 35% and 70% lower insulin sensitivities at BMI 28 and 35 kg/m2, respectively. After adjusting for truncal-abdominal sc fat distribution, which was more pronounced in the women with PCOS, the two groups had similar insulin sensitivity over the entire range of BMI (P = 0.9), whereas the difference in insulin increment was insignificant after adjusting for the free androgen index (testosterone x 100/sex hormone binding globulin; P = 0.16). Hemoglobin A1C levels were lower in women with PCOS than in the control subjects. It is concluded that the early insulin response to glucose was increased in women with PCOS, not accounted for by insulin resistance, closely associated to the increased androgenicity, and present also at low-normal BMI. In contrast, insulin resistance was seen only at higher BMI levels and was largely determined by the increased truncal-abdominal fat mass in PCOS.