Estrogen receptors in breast tumors were assayed in 55 premenopausal women undergoing bilateral oophorectomy and in 120 postmenopausal women undergoing bilateral adrenalectomy for treatment of metastatic breast cancer. The data show that 20 (60%) of the 32 patients with estrogen receptor-positive (ER+) tumors had objective remission after oophorectomy, and 44 (51%) of the 87 patients with ER+ tumors responded to adrenalectomy. In contrast, of those patients with estrogen receptor-negative (ER-) tumors, only 3% had an objective remission following oophorectomy and 9% following adrenalectomy. It is concluded that major endocrine ablative procedures are not justified in patients with ER- tumors. The data also conclusively demonstrate the significance of 4S receptors in predicting the response to endocrine therapy. In this study, it was found that although the response rate to endocrine ablation was substantially higher (71-83%) in patients whose tumors contained both estradiol and progesterone receptors, between 50 and 60% of ER+ tumors lacking progesterone receptors had objective remission after endocrine ablative therapy.