The effects of 17beta-estradiol (E2) on sympathetic activity were examined in conscious unrestrained ovariectomized rats, instrumented under methohexital anesthesia to record mean arterial pressure (MABP), heart rate (HR), renal nerve activity (RNA), and splanchnic nerve activity (SNA) 1 day before the experiment. Injection of E2 (150 micrograms/kg iv) caused reductions (P < 0.01) in RNA (29 +/- 6%), SNA (25 +/- 2%), and HR (26 +/- 5 beats/min) within 20 min, but MABP remained unchanged. Ninety minutes after intravenous injection of E2 or vehicle, intravenous infusion of phenylephrine (PE; 6.2 micrograms . min-1 . kg-1) induced similar increases in MABP and decreases in HR, RNA, and SNA in both groups. By contrast, in rats chronically treated with E2, the pressor response to PE was smaller (P < 0.01; 22 +/- 5 mmHg) than in vehicle-treated rats (40 +/- 4 mmHg). The changes in HR, RNA, and SNA were similar in both groups, but the ratios of changes in HR and SNA to MABP, an index of baroreflex sensitivity, were greater in the E2-treated rats. These findings suggest that E2 can act centrally to modulate sympathetic function and thereby participate in cardiovascular regulation.