Antiestrogens are established as compounds which predominantly exert their actions by competing with estrogen for binding to the target steroid receptor. This is evidenced by the observations that their biological effects are most notably recognised in tissues that contain ER; they often structurally resemble estrogens in regions which are important for the binding of the steroid nucleus to the ER and their ER binding, while of differing efficiency, always displaces and/or prevents the association of estrogens (Nicholson, 1993). Simplistically, as a consequence of such binding, antiestrogens subsequently reduce estrogen signalling within responsive cells. In practice, however, they display a bewildering diversity of biological properties, with tissue-specific actions that are not easily reconciled with such a basic model (Furr and Jordan 1984; Nicholson et al. 1986). Thus, while the non-steroidal triph-enylethylene compound tamoxifen (the most widely prescribed antiestrogenic drug used in the therapy of breast cancer) promotes objective tumour remissions in approximately 30–50% of women (presumably an antiestrogenic response), it shows many estrogen-like characteristics on endometrium, bone and the cardiovascular system (Powles 1997). Indeed, long-term tamoxifen therapy, while delaying the recurrence of primary breast cancer and reducing the incidence of contralateral cancers (Early Breast Cancer Trialist’s Collaborative Group 1992), promotes a significant increase in the development of endometrial cancers (presumably an estrogenic response; Cohan 1997), with possible additional detrimental effects on the liver (Wogan 1997).