The presence of the renin-angiotensin system (RAS) in extrarenal tissues, namely the vascular wall and brain tissue, is well established. The availability of effective blocking agents, converting-enzyme inhibitors, has made it possible to further elucidate important functions of the extrarenal RAS. We have found that the angiotensin converting-enzyme inhibitor captopril shifts the limits of cerebral blood flow autoregulation to lower blood pressure levels in normotensive and in spontaneously hypertensive rats. This effect may explain our finding of a remarkable preservation of cerebral blood flow, despite significant blood pressure reduction, in patients with chronic heart failure. We suggest that the effect of angiotensin converting-enzyme inhibition on autoregulation of cerebral blood flow is mediated by a dilatation of larger cerebral arteries, which results from inhibition of the vascular tone normally maintained by locally produced angiotensin II.