The effect of central administration of angiotensin II (ANG II) on efferent renal sympathetic nerve activity (RSNA) was studied in conscious sheep. ANG II (1 nmol/h), infused for 30 min into the lateral cerebral ventricles in five sheep, did not alter mean arterial pressure (MAP) but reduced RSNA to 38 +/- 5% of control. Intracerebroventricular infusion of higher doses of ANG II (3 and 10 nmol/h), which increased MAP by 12 +/- 2 and 14 +/- 3 mmHg, respectively, reduced RSNA to 9 +/- 5 and 11 +/- 7% of control. MAP and RSNA gradually returned to control over a period of 2 h after the infusions. Intracerebroventricular losartan (1 mg/h for 1 h before, and then during, angiotensin infusion) blocked all the effects of angiotensin (3 nmol/h). Baroreflex relationships constructed from the beat-to-beat relationship of RSNA to diastolic pressure showed a significant leftward shift during intracerebroventricular ANG II compared with the control relationship. The beat-to-beat relationship between central venous pressure and RSNA was abolished during intracerebroventricular infusion of ANG II. These findings demonstrate that intracerebroventricular ANG II has a direct central inhibitory action on RSNA that is independent of both arterial and low-pressure baroreceptors. This effect of angiotensin is mediated by central angiotensin AT-1 receptors.