The endothelin-B receptor (ETR) mediates vasodilation in young women, an effect that is absent in postmenopausal women. We have previously demonstrated that ETR-mediated vasodilation is regulated by estradiol (E) in young women; however, the impact of E on ETR function in postmenopausal women remains unknown. Accordingly, the objective of this study was to test the hypothesis that E exposure restores ETR-mediated dilation in postmenopausal women. Ten healthy postmenopausal women (55 ± 2 yr of age, 5 ± 3 years since menopause) completed the study. E was administered by transdermal patch for 7 days (0.1 mg/day, Vivelle-Dot patch). Vasodilation in the cutaneous microcirculation (microvascular endothelial function) was measured via local heating (42°C) using laser Doppler flowmetry combined with intradermal microdialysis perfusions of lactated Ringer's (control) and ETR antagonist (BQ-788, 300 nM) at baseline and after E administration. There was no effect of E on ETR function [hormone × site, (1,9) = 0.77, = 0.40]. These data demonstrate that in contrast to findings in premenopausal women, E administration does not restore ETR function in postmenopausal women. The vascular endothelial endothelin-B receptor (ETR) mediates vasodilation in premenopausal women, an effect modulated by estradiol. ETR-mediated vasodilation is lost in postmenopausal women, but the effect of exogenous estradiol administration on ETR function in postmenopausal women is not known. During estradiol administration, ETR blockade did not affect cutaneous microvascular vasodilatory response to local heating. We demonstrate that exogenous estradiol administration does not restore ETR-mediated vasodilation in postmenopausal women.