Aminoglutethimide and dexamethasone were administered for 3 months to 11 postmenopausal women with advanced breast cancer. During initial in-hospital studies, there was uniform suppression of plasma cortisol (0.23 microgram/100 ml), androstenedione (8.3 ng/ 100 ml), estrone (0.44 ng/100 ml), and estradiol (0.32 ng/100 ml) to concentrations indistinguishable from those after surgical adrenalectomy. Eight of the 11 patients maintained this degree of suppression for 3 months. The other three patients may have taken inadequate amounts of dexamethasone, as evidenced by plasma steroid patterns characteristic of aminoglutethimide alone, that is, partial cortisol suppression (3.6 microgram/100 ml) and markedly increased androstenedione (355 ng/100 ml) with low estrone (0.54 ng/100 ml) and estradiol (0.61 ng/100 ml) concentrations. This apparent block in the aromatization of androstenedione to estrogens may be a feature important to the effectiveness of the regimen in sporadically noncompliant patients. After 3 months of therapy, return of resting plasma cortisol values to normal occurred within 3 to 4 days after cessation of the regimen and pituitary-adrenal responsiveness to surgical stress was demonstrable. This regimen is capable of maintaining an effective, reversible suppression of plasma steroids considered to be relevant to estrogen-dependent breast cancer.