Inhibition of estrogen production results from oophorectomy, adrenalectomy and hypophysectomy. These are all major surgical procedures that have an attendant morbidity and mortality. The ability to accomplish the same end by a well tolerated antiestrogen like tamoxifen is a desirable objective. Additive hormone therapy, particularly with estrogens, likewise has its side effects of menstrual bleeding, gastrointestinal disturbances and weight gain. Nafoxidine produces a higher response rate than estrogen administration (31% vs. 14%). Estrogen antagonists may become more important in hormonal therapy of breast cancer in premenopausal and postmenopausal women. Few data are available on the relation of estrogen receptor content of the tumor and response to estrogen antagonists. Other clinical trials underway are testing the relative effectiveness of antiestrogen treatment added to combination chemotherapy, or in place of surgical oophorectomy, adrenalectomy or both. The results from these trials will add to knowledge on the biology of breast cancer, as well as the possibility of improving the well being of patients. The finely tuned and specific regulation of cell growth by a chemical rather than the use of pharmacologic doses of hormones or major surgical procedures approaches the true aim of disease therapy, namely, specificity and minimal toxicity.