Estrogen receptors (ER) were measured on specimens taken from 27 patients with benign breast conditions and 109 patients with breast cancer. Using sucrose gradient assay, 15% (4/27) of benign lesions and 56% (61/109) of malignant tumors were estrogen receptor-positive (ER-positive means 8S or 8S+4S levels more than 7 fmoles/mg cytosol protein). Progesterone receptors (PR) were tested on specimens from 28 patients and 39% (10/26) of the cancers were PR-positive. ER protein activity was not correlated with stage, histology, size of primary lesions, or extent of axillary or distant metastasis. Tumors with low ER levels are more likely to recur, and recurrent tumors after longer disease-free intervals are more likely to be ER-positive. Detailed analysis showed that ER levels did correlate with age and serum albumin levels. Concentrations of serum alpha1-globulin were decreased, while IgG and IgM were significantly increased among patients with positive ERs. Eighteen evaluable patients with advanced breast cancer had endocrine therapy, 13 had objective response. Twelve of these 13 had 8S receptor above 10 fmoles/mg, or 4S above 15 moles/mg, or 8S+4S above 25 fmoles/mg. The one exceptional patient had tumor with high PR but without detectable ER.