It has been shown that reactive oxygen species (ROS) contribute to the central effect of ANG II on blood pressure (BP). Recent studies have implicated an anti-hypertensive action of estrogen in ANG II infused female mice. The present study used in vivo telemetry recording and in vitro living mouse brain slices to test the hypothesis that central activation of estrogen receptors in male mice inhibits ANG II-induced hypertension via modulation of central ROS production. In male wild-type mice, systemic infusion of ANG II induced a significant increase in BP (30.1±2.5 mmHg). Either central infusion of tempol or 17-estradiol (E2) attenuated the pressor effect of ANG II (10.9±2.3 and 4.5±1.4 mmHg), and the protective effect of E2 was prevented by co-administration of an estrogen receptor, antagonist ICI182,780 (ICI, 23.6±3.1 mmHg). Moreover, ganglionic blockade on day 7 after ANG II infusions resulted in a smaller reduction of BP in central tempol and in central E2 treated males suggesting that estrogen inhibits central ANG II-induced increases in sympathetic outflow. In subfornical organ slices, application of ANG II resulted in a 21.5±2.5% increase in ROS production. Co-administration of irbesartan, an angiotensin Type 1 receptor antagonist, or pre-incubation of brain slices with tempol blocked ANG II-induced increases in ROS production (-1.8±1.6% and -1.0±1.8%). The ROS response to ANG II was also blocked by E2 (-3.2±2.4%). The results suggest that the central actions of E2 are involved in protection from ANG II-induced hypertension and that estrogen modulation of ANG II-induced effects may involve interactions with ROS production.