Objective: We sought to determine whether raloxifene increases coronary and uterine blood flow in ovariectomized ewes. Study Design: Twelve ewes were chronically instrumented for measurement of mean arterial pressure, heart rate, cardiac output, coronary blood flow, and uterine blood flow. Sheep received 17β-estradiol, Estrace, raloxifene, or KY Jelly vehicle on separate days. Results: 17β-Estradiol increased uterine blood flow from 21 ± 3 to 254 ± 36 mL/min and coronary blood flow by 21% ± 2% within 2 hours. Estrace increased uterine blood flow from 30 ± 7 to 260 ± 62 mL/min and coronary blood flow by 8% ± 4% within 3 hours. Raloxifene increased uterine blood flow from 20 ± 3 mL/min to 220 ± 53 mL/min by 6 hours and coronary blood flow by 22% ± 5% within 24 hours. To determine whether hemodynamic responses were mediated by nitric oxide, L -nitroarginine methyl ester was administered and produced an approximate 50% decrease in uterine blood flow for all 3 compounds. L -Nitroarginine methyl ester attenuated increases in coronary blood flow induced by 17β-estradiol, Estrace, and raloxifene. Conclusion: Raloxifene has significant coronary and uterine vascular effects in the ovariectomized ewe. The coronary and uterine responses are partially mediated by nitric oxide. (Am J Obstet Gynecol 2000;182:521-8.)