Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U46619 were given doses (0.01-30μM) of 17Β-estradiol in the presence and absence of endothelium and these inhibitors: 10μM indomethacin (cyclooxygenase inhibitor), 10μM methylene blue (inhibits soluble guanylate cyclase), 100μM nitro-L-arginine (inhibits nitric oxide synthesis), 100μM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30μM mifepristone (Ru38486 steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30μM), elicited an acute dose-dependent relaxation of bovine coronary arteries from 4%-68% (n=15). No major difference in relaxation was observed between coronary arteries with or without endothelium, indicating that the mechanism was endotheliumindependent. Indomethacin, nitro-L-arginine and methylene blue did not alter this relaxation, suggesting that relaxant prostaglandins, 1-arginine products and cGMP are not involved (n=11-16), isobutylmethylxanthine enhanced relaxation from 20%-40% (n=15 p<0.01), suggests a role for cAMP. Furthermore, mifepristone reduced the relaxation by more than 50% (n=15 p<0.05) consistent with the role for estrogen receptors. Based on our study, estrogen causes a dosedependent relaxation of bovine coronary arteries that does not appear to utilize endothelium, prostaglandins, cGMP or arginine products, but may involve cAMP and estrogen receptors. This study may help justify treating myocardial ischemia with estrogen.