Deterioration in glucose tolerance occurs rapidly in women with PCOS, suggesting that pancreatic -cell dysfunction may supervene early. To determine if the compensatory insulin secretory response to an increase in insulin resistance induced by the glucocorticoid dexamethasone differs in women with PCOS and Controls, we studied 10 PCOS and 6 Controls with normal glucose tolerance. An OGTT and a graded glucose infusion (GGI) protocol were performed at baseline and after taking 2.0 mg dexamethasone orally. Basal (_b), static (_s), dynamic (_d), and global ( indices of -cell sensitivity to glucose were derived. Insulin sensitivity (Si) was calculated using the minimal model; a disposition index (DI) was calculated as the product of Si by . PCOS and Controls had nearly identical fasting and 2 hr glucose levels at baseline. _b was higher, although not significantly so, in the PCOS subjects. The _d, _s, and indices were 28%, 19%, and 20% higher, respectively, in PCOS subjects. The DI was significantly lower in PCOS (30.01 ± 5.33 vs. 59.24 ± 7.59) at baseline. After dexamethasone, Controls averaged a 9% increase (to 131 ± 12 mg/dl) in 2 hr glucose levels; women with PCOS had a significantly greater, 26% increase to 155 ± 6 mg/dl. The C-peptide: glucose ratios on OGTT increased by 44% in Controls and by only 15% in PCOS. The accelerated deterioration in glucose tolerance in PCOS may result, in part, from a relative attenuation in the response of the -cell to the demand placed on it by factors exacerbating insulin resistance.