To determine whether insulin resistance occurs in polycystic ovarian disease (PCO) in the absence of obesity and acanthosis nigricans, circulating levels of insulin in response to oral glucose administration were measured in 10 nonobese PCO patients without acanthosis nigricans and in 10 normal women matched for weight and height. Mean serum testosterone (T), androstenedione (A), dehydroepiandrosterone (D), D sulfate, and LH levels were significantly elevated in the PCO patients compared to those in control subjects. In PCO patients, the mean +/- SE basal insulin level (18.7 +/- 2.9 microU/ml) and the sum of the insulin levels in response to glucose (674 +/- 119 microU/ml) were significantly greater than those in the control group (11.0 +/- 0.8 microU/ml and 248 +/- 29 microU/ml, respectively). In all subjects, serum levels of T and A, but not D and D sulfate, were significantly correlated to basal insulin levels and insulin sums. Serum cortisol, GH, and PRL levels were similar in both groups. These results indicate that in PCO, a significant degree of insulin resistance exists, which clearly is not related to obesity. The positive correlation of serum T and A levels to circulating insulin levels in this study suggests that the insulin resistance in PCO may be, in part, a consequence of hyperandrogenism.