We examined the role of nitric oxide (NO) in autoregulation of cerebral blood flow (CBF) in the rat. Autoregulation of the CBF is defined as the physiological tendency of the brain to maintain a constant CBF despite changes in arterial blood pressure (ABP). Male Sprague-Dawley rats were divided into six groups: a saline group (n = 9), a saline + hypotension group (n = 8), an N-G-monomethyl-L-arginine (L- NMMA) group (n = 7), an L-NMMA + hypotension group (n = 9), a denervation group (n = 6), and a denervation + hypotension group (n = 15). We employed the [C-14]iodoantipyrine method to measure CBF. In each hypotension group, the ABP was lowered by withdrawing blood. In each L-NMMA group, 30 mg/kg of L-NMMA, a potent NO synthase (NOS) inhibitor, was injected intravenously before making the CBF measurement. In each denervation group, unilateral chronic transection of the perivascular NOS-containing nerve fibers was performed at 2 weeks before the CBF measurement, We found a significant impairment of autoregulation in the L-NMMA and L-NMMA + hypotension groups, whereas the saline and saline + hypotension groups as well as the denervation and denervation + hypotension groups did not show any definite disturbance of autoregulation. We infer that NO, probably derived from the vascular endothelium, may play an important role in autoregulation of CBF.