The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (ALDO; 1.8 µg/kg/h, 1% NaCl to drink, 28 days) and that central estrogen plays a protective role against the development of hypertension. In rats with blood pressure (BP) and heart rate (HR) measured by DSI® telemetry, chronic ALDO/NaCl treatment induced a greater increase in BP in males (25.4±2.4 mmHg) than in females (7.1±2.2 mmHg). Gonadectomy augmented ALDO/NaCl-induced hypertension in females (18.2±2.0 mmHg) but had no effect in males (23.1±2.9 mmHg). Immunohistochemistry for Fra-like activity was higher in the paraventricular nucleus of intact males, castrated males and ovariectomized (OVX) females compared to intact females after 28 days of ALDO/NaCl treatment. In intact males, central 17-estradiol (E2) inhibited the ALDO/NaCl increase in BP (10.5±0.8) compared to that in central vehicle plus systemic ALDO/NaCl (26.1±2.5 mmHg) rats. Combined administration of E2 and estrogen receptor antagonist ICI182,780 (ICI) blocked the protective effect of E2 (23.2±2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the ALDO/NaCl (20.4±1.8 mmHg) BP increase. Lastly, ganglionic blockade after ALDO infusions resulted in a smaller reduction in BP in intact females (-23.9±2.5 mmHg) and in central estrogen-treated males (-30.2±1.0 mmHg)as compared with other groups (intact males 39.3±3.4, castrated males 41.8±1.9, intact males with central E2+ICI 42.3±2.1, OVX females 40.3±3.3, intact females with central ICI 39.1±1.3 mmHg). Chronic ALDO infusion produced increases in NaCl intake and decreases in HR that were both similar in all groups. Taken together the results indicate that central estrogen plays a protective role in the development of ALDO/NaCl-induced hypertension and that this may result from reduced sympathetic outflow.