From a review of clinical material, relationships were investigated between tumor estrogen receptors (ER) in breast cancers and (1) response of metastases to chemotherapy or endocrine therapy in 54 patients and (2) prognosis after mastectomy in 274 patients. Considering more than 300 femtomoles of ER per gram of tissue ER "rich" for premenopausal women and more than 700 ER rich for postmenopausal women, 14 of 20 patients (70%) with ER-rich tumors responded to endocrine therapy, whereas only one of 21 (4.8%) with ER-poor tumors responded. The probability of response appeared to increase with the concentration of ER. No correlation could be found between ER status and responsiveness to chemotherapy. Compared with patients with primary tumors poor in ER, those with ER-rich tumors had less recurrence after mastectomy, a longer free interval, and a more favorable disease-free survival, The 8S and 4S fractions of ER had similar relationships to tumor response and prognosis.