The present experiments sought to identify brain regions in which implants of an antiestrogen would antagonize the ability of a systemic estradiol treatment to activate sexual behavior in female rats. In experiment 1, ovariectomized female rats were implanted subcutaneously with 5-mm Silastic capsules containing a 5% concentration of estradiol and injected with 500 micrograms progesterone 2 days later, 4-5 h before testing for sexual behavior. Bilateral intracranial implants of 1% crystalline concentrations of the high-affinity antiestrogens monohydroxytamoxifen (TAM) or keoxifene placed into the ventromedial nucleus of the hypothalamus (VM) 24 h prior to estradiol treatment significantly reduced lordosis responsivity compared with control females receiving empty cannulae. Implants of 1% TAM into the medial preoptic area or medial amygdala 24 h prior to estradiol that no significant effect on lordosis. Similarly, implants of 1% TAM into the VM 12 h after estradiol had no effect on lordosis. In experiment 2, lordosis was activated by subcutaneous implants of Silastic capsules containing 1% estradiol plus 500 micrograms progesterone. In this experiment, implants of 1% TAM into the VM 24 h prior to estradiol significantly reduced lordosis only if both cannulae tips were in, or adjacent to, the VM. Females receiving intracranial 1% TAM, but whose cannulae (even unilaterally) were outside the VM, had levels of lordosis equivalent to those of control females. Increasing the concentration of intracranial TAM to 10% virtually eliminated lordosis in females with bilateral implants in the VM, whereas females receiving intracranial 10% TAM in the region of, but outside, the VM showed no evidence of a lordosis deficit.(ABSTRACT TRUNCATED AT 250 WORDS)