In the present study, the effects of 17 beta-estradiol on vascular reactivity of ovariectomized rats and proliferation of cultured rat aortic smooth muscle cells were studied. The vascular reactivity was significantly increased in ovariectomized rats compared with the sham-operated animals. The selective ETA receptor antagonist BQ123 inhibited the increase in [3H]-TdR incorporation in response to ET-1 on vascular smooth muscle cells (VSMCs). 17 beta-estradiol also attenuated the ET-1 effects in a dose-dependent manner. The results of RT-PCR and Western blot show that expression of ETA receptor was decreased after treatment with 17 beta-estradiol. The effect of 17 beta-estradiol was partially inhibited by estrogen receptor antagonist tamoxifen. The above results demonstrate that proliferation of VSMCs stimulated by ET-1 was mainly mediated through ETA receptor. Due to the down-regulation of ETA receptor and mediation of estrogen receptor, 17 beta-estradiol inhibits the ET-1-induced proliferation of VSMCs and decreases the vascular reactivity of ovariectomized rats.