Hormonal changes induced by the pure antiandrogen flutamide were studied in three postmenopausal metastatic breast cancer patients. The drug was administered at a dose of 250 mg, three times a day for 3-6 months. In each patient a sharp decrease of about 50% was observed in the circulating levels of DHT and DHEAS, irrespective of pretreatment values. A concomitant, although less pronounced, reduction in circulating testosterone, androstenedione and estradiol was found. A decrease in circulating steroids was associated with a 30% decrease in SHBG concentrations in two patients; in the third patient a 30% increase occurred. Androgens in urine, namely testosterone, androstanediol and 17-KS, decreased accordingly. In addition, a marked decrease in 17-OHCS occurred in two of the patients. These data indicate that flutamide is an effective antiandrogen in women and suggest two possible mechanisms by which the drug exerts its antiandrogenic activity: (a) inhibition of conversion of testosterone into the more active DHT, and (b) inhibition of synthesis of the adrenal precursors of active androgens. Minor variations in circulating LH and FSH were observed. Pretreatment prolactin values, which were higher than normal, dramatically decreased by 90% in one patient who had a partial remission of her disease, and they further increased in another patient who relapsed while on therapy.