To determine the effect of aromatase inhibitors on peripheral aromatization, male rhesus monkeys were infused with [7-3H]androstenedione and [4-14C]estrone before and during treatment with 4-hdyroxy-androstene-3,17-dione (50 mg/kg each; four monkeys) or 4-acetoxy-androstene-3,17-dione (700 mg each; two monkeys). In all six monkeys, no specific effects on the MCRs of androstenedione and estrone, the interconversion of androgens or estrogens, or androstenedione conversion to dihydrotestosterone were noted. In five of the six animals, aromatization rates were reduced by up to 97% of control values. The results demonstrate that these compounds inhibit peripheral aromatization and, together with our other results, suggest that aromatase inhibitors may be a useful treatment for estrogen-dependent cancer.