It has been reported in women with polycystic ovary syndrome (PCOS) that LH secretion is not altered by insulin infusion. To determine whether insulin resistance may have precluded an effect of insulin, pulsatile LH secretion and gonadotropin responses to GnRH were examined in PCOS women (n = 9) before and after pioglitazone treatment (45 mg/d) for 20 wk in the presence and absence of a hyperinsulinemic euglycemic clamp (80 mU/m2.min). Frequent blood samples were obtained for 12 h (every 10 min) as well as during sequential administration of GnRH at doses of 2, 10, and 20 microg over 12 h. A significant (P < 0.05) improvement in insulin sensitivity was seen in the subjects after treatment. Mean LH levels, LH pulse frequency and amplitude, as well as gonadotropin responses to GnRH were not influenced by pioglitazone, either with or without insulin infusion. We conclude that in PCOS women, inappropriate gonadotropin release does not appear to be a consequence of hyperinsulinemia.