Numerous reports demonstrate the potency of estrogens to modulate brain function and their implications in schizophrenia and depression. The 5-HT(1A) receptor has been suggested to be implicated in depression and anxiety. Selective estrogen receptor modulators (SERMs), like tamoxifen and raloxifene, have estrogenic and/or antiestrogenic activity depending on the target tissue. Hence, SERMs have beneficial effects in skeleton and cardiovascular systems but act as antagonists in breast and uterus. The aim of the present study was thus to investigate in ovariectomized rats the effects of 17beta-estradiol, tamoxifen and raloxifene treatments on 5-HT(1A) receptor binding sites (agonist and antagonist) and mRNA levels in the hippocampal formation, prefrontal and cingulate cortex, as well as dorsal raphea nucleus which are known to express estrogen receptors (ER). Two weeks ovariectomy of female rats led to a 60% decrease of uterine weight, which was prevented by a 2-week 17beta-estradiol treatment; tamoxifen and raloxifene increased uterine weights by 35% and 15%, respectively, but significantly less than estradiol treatment. Specific binding to 5-HT(1A) receptors was determined by autoradiography of brain sections using the selective ligands: [3H]8-OH-DPAT and [3H]MPPF. Ovariectomy and hormone replacement therapy did not significantly affect 5-HT(1A) receptor agonist and antagonist specific binding sites as well as mRNA levels in all subregions of the hippocampus, prefrontal and cingulate cortex as well as dorsal raphea nucleus. Although the present treatments had functional effects as assessed with uterine weights, ovariectomy and estrogen-receptor directed drugs had no effect on hippocampal 5-HT(1A) receptors as compared to 5-HT(2A) receptors previously reported.