The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid ¹³³-Xe method while blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 hours. Five groups of animals were studied: 1): Nephrectomized dialyzed rats, 2): nephrectomized dialyzed rats given a single dose i.v. of the angiotensin converting enzyme inhibitor captopril (10 mg/kg), 3): sham nephrectomized and dialyzed rats, 4): rats receiving drugs as dialyzed rats but no surgery, 5): rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared to controls. Nephrectomy, captopril, sham operation or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53±-4 mmHg) and sham-operated (58±-4 mmHg) rats, compared to diet control rats (78±-3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35±-2 mmHg). Thus, removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin, and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls.