The present experiments investigate whether the absence of tachycardia during lowering of blood pressure (BP) with an angiotensin-converting enzyme inhibitor (CEI) in salt-depleted dogs is due to an alteration in the activity of the baroreflex. Baroreflex activity was measured after pharmacological manipulation of BP using intravenous nitroglycerin or phenylephrine, and the heart period (R-R interval) relative to the arterial pressure pulse was recorded. The slope of the relationship between BP and R-R interval is a measure of the sensitivity of the baroreceptor reflex and displacement of the line indicates a change in the setpoint of BP. On normal sodium diet, the sensitivity and setpoint of the baroreflex were unaltered by the nonapeptide CEI given both intravenously and into a lateral cerebral ventricle. During salt depletion. however, intravenously but not centrally administered CEI altered the setpoint of the baroreflex without modifying the sensitivity. The alteration in the setpoint that occurred following intravenous CEI in the salt-depleted dog could well account for the fact that the fall in BP induced by CEI does not cause reflex tachycardia. These results indicate that circulating but not brain angiotensin II is essential for the maintenance of baroreflex function during sodium depletion and provide further evidence for the important interactions between angiotensin and the autonomic nervous system.