The endocrinological and clinical effects of an LH-RH agonist, Zoladex, and an antiestrogen, Nolvadex, in patients with advanced breast cancer are outlined and their potential in the therapy of nonmalignant diseases of the breast and high-risk states is briefly discussed. Additional data are presented to indicate that new antiestrogens are now available for experimental studies that, unlike tamoxifen, do not possess partial estrogen-like activity and that show favorable antitumor properties against DMBA-induced mammary tumors and MCF-7 human breast cancer cells in culture. The lack of agonistic effects of this new class of pharmacological agents now allows a state of total estrogen deprivation to be approached, a previously unobtainable clinical goal.