Fasting insulin concentrations and the insulin response to an oral glucose tolerance test were measured in six virilized women with ovarian hyperthecosis and six weight-matched normal women. For comparison, six women with polycystic ovarian disease were also studied. The diagnosis of hyperthecosis was confirmed in all six virilized women by histologic examination of the ovaries. The fasting insulin concentrations were increased in all of the hyperthecosis patients (84 +/- 32 microU/ml). Insulin response to an oral glucose tolerance test was greatly increased (p less than 0.01) in comparison to normal women and women with polycystic ovarian disease. Significant positive correlations were found between peripheral insulin concentrations and ovarian vein testosterone (r = 0.879, p less than 0.02), dihydrotestosterone (r = 0.866, p less than 0.03), and androstenedione (r = 0.992, p less than 0.01) levels. Insulin resistance persisted after removal of the ovaries even though androgen levels returned to normal. These results suggest that a significant degree of insulin resistance exists in women with hyperthecosis and that insulin stimulates ovarian stromal androgen synthesis and thus may play a role in the pathogenesis of ovarian hyperthecosis.