Ovariectomized CFW mice were treated with tamoxifen (TAM) alone or in combination with estradiol benzoate (EB) to determine its ability to promote/block lordotic behavior and the induction of hypothalamic progestin receptors (PR). Across a range of doses, TAM plus progesterone treatment did not activate female sexual behavior. When given with EB, TAM suppressed lordotic behavior in a dose-dependent fashion. TAM did not induce PR when given alone and it completely blocked the ability of EB to induce PR. It therefore appears that for these responses TAM functioned as a pure antagonist in the female mouse brain, although the degree of its antiestrogenicity varied with the response under consideration. A potential mechanism mediating this differential effectiveness is discussed.