Toremifene, a new antiestrogenic antitumor compound, has several biologically active metabolites. The hormonal effects of the main metabolites resemble those of unchanged toremifene. The main metabolite in humans, N-demethyltoremifene, is bound to estrogen receptors (ER), inhibits the growth of MCF-7 cells, and exerts an antiestrogenic effect similar to that of toremifene. However, its antitumor effect in vivo against dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancers is weaker than that of toremifene. Didemethyltoremifene has antiestrogenic actions in mouse and rat uterus at high doses. 4-Hydroxytoremifene is bound to ER with higher affinity and inhibits MCF-7 growth at concentrations lower than those of toremifene. It has a weaker intrinsic estrogenic effect than does toremifene. The efficacy of 4-hydroxytoremifene against DMBA-induced cancers is weak except at very high doses. Oxidations of N-demethylated metabolites to (deamino)hydroxylated compounds and carboxylic acids are the detoxification routes of toremifene. (deaminohydroxy)Toremifene has only weak hormonal actions at high doses and carboxylated metabolites have no estrogenic/antiestrogenic effects. The antitumor effect of toremifene in vivo is mainly due to unchanged toremifene, but hormonal effects (which may have a role in antitumor actions) are partly attributable to metabolites N-demethyltoremifene, didemethyltoremifene, (deaminohydroxy)toremifene, 4-hydroxy-N-demethyltoremifene, and 4-hydroxytoremifene, which have pharmacological properties similar to those of toremifene.