To determine if delta 1-testololactone can inhibit the peripheral aromatization of androstenedione (delta), nine postmenopausal women with metastatic breast cancer were studied before and after 2 weeks of therapy with 250 mg of the drug, given every 6 h by mouth. The conversion ratio of delta to estrone (E1) was significantly reduced (P less than 0.005) from a mean (+/-SE) of 0.0098 +/- 0.0025 before to 0.0009 +/- 0.0005 after treatment. The drug's effect on the metabolism of delta seemed to be specific since significant changes in the MCR of delta and in the conversion ratio to testosterone were not observed. That this inhibition of peripheral aromatization had an effect on E1 metabolism was shown by the significant decrease (P less than 0.01) of mean serum E1 levels from 22 +/- 3 pg/ml before to 12 +/- 1 pg/ml after treatment. Serum estradiol levels rose slightly from 8 +/- 0.8 to 12 +/- 4 pg/ml. Serum delta and testosterone levels were unchanged by therapy. These data are consistent with the concept that delta 1-testololactone is a potent inhibitor of peripheral aromatization of delta to E1. This mechanism could explain the antitumor properties of this compound.