One hundred nine pre- and postmenopausal mammary carcinoma cases were studied to elucidate the role of sex hormone binding globulin (SHBG) in the hormone dependence of human breast cancer. Our findings indicate that there is a significant negative correlation between SHBG binding capacity and plasma testosterone concentration. All patients with high SHBG titers were found to be cytosol estrogen receptor (CER) positive and the plasma SHBG binding capacity of CER positive was significantly higher than that of CER negative patients. We also found that the level of pretherapy plasma SHBG concentration is a reliable indicator in predicting the efficacy of hormone therapy. Our findings also confirm that, for a tumor to be hormone dependent, high plasma SHBG concentration and estrogen receptors must be present simultaneously. The present pretherapy determination of SHBG titers is easier and more reliable than previous methods for determining the hormone dependence of human breast tumors.