Surgical adrenalectomy produces objective tumour regression in 50-60% of estrogen receptor-positive women with metastatic breast carcinoma. Additional responses to antiestrogens or further suppression of estrogens with aminoglutethimide after adrenalectomy suggest the possibility of continued adrenal steroid secretion even after surgical ablation. The use of sensitive and specific RIAs allows precise determination of the degree of hormone suppression after adrenalectomy and could provide documentation of nonsuppression or escape from suppression in individual patients. To evaluate the possibility of continued hormone secretion, we measured 14 hormones in 26 postmenopausal women with breast carcinoma before and after adrenalectomy. While the mean levels of androgens were markedly suppressed [dehydroepiandrosterone sulfate (DHEA-S), 99%, androstenedione, 94%; testosterone, 77%; dihydrotestosterone, 73%] after adrenalectomy, estrogen concentrations fell to a much lesser extent (plasma estrone, 73%; urinary estrone, 86%; plasma estradiol, 53%; urinary estradiol, 67%). Examination of data in individual patients revealed incomplete suppression in several women (less than 50% suppression of plasma estradiol in 14 of 25 patients, of urinary estradiol in 4 of 22, and of urinary estrone in 1 of 22). Androgen concentrations also fell incompletely after adrenalectomy in a few patients. Androstenedione concentrations were greater than 2 SD above the group mean in 2 of 23 patients, and in 2 of 25 patients, DHEA-S concentrations were also greater that 2 SD above the group mean. Serial measurements of hormones over a 1- to 3-yr period following surgery revealed escape from suppression over time (i.e. greater than 2-fold increase in hormone levels) in 7 of 26 women. The practical significance of the lack of suppression or of escape from inhibition was assessed by comparing estrogen levels in responders vs. nonresponders to surgical adrenalectomy. Of all steroids measured, greater suppression of only 1 hormone (urinary estrone) was observed in responders vs. nonresponders. These data indicate that adrenalectomy does not uniformly suppress circulating androgen and estrogen levels in postmenopausal patients. Women who initially suppress after adrenalectomy may show recovery of either androgen or estrogen levels with time.