Plasma levels of estrone and estrone sulfate were measured in 16 postmenopausal women with advanced breast cancer before and during chronic aminoglutethimide therapy. Aminoglutethimide caused a significant reduction in plasma estrone (mean 36%, P less than 0.025) and estrone sulfate (mean 65%, P less than 0.001). The estrone/estrone sulfate ratio was increased by a mean of 84% (P less than 0.0025). These results suggest that aminoglutethimide influences plasma estrone sulfate by mechanisms unrelated to aromatase inhibition. The findings in this study are consistent with previous results suggesting that aminoglutethimide treatment enhances the rate of estrone sulfate metabolism. This biochemical effect of aminoglutethimide treatment could be a contributory factor to the drugs mechanism of action.