Effect of nitric oxide (NO) on vasomotor tone of cerebral parenchymal arterioles was studied in rats. Then, the role of NO was clinically investigated in the pathogenesis of progressive cerebral vascular occlusive disease, moyamoya disease. In rat, the cerebral arterioles, about 30-60 microm in diameter, were dilated by L-arginine, a precursor of NO, at concentrations as low as 0.1 micromol with maximal dilation of 14% at 100 micromol. The arterioles were constricted by N(G)-monomethyl-L-arginine (L-NMMA), a NO synthesis inhibitor. Superoxide dismutase, which seems to protect NO from inactivation, increased sensitivity of L-arginine. Compared with control specimens of cerebral spinal fluid (CSF) obtained from 16 patients, concentrations NO metabolites in the CSF of 23 patients with moyamoya disease were significantly higher. NO metabolites concentrations obtained during initial surgery decreased during a second, contralateral procedure. NO plays an important role in the regulation of basal tone of cerebral parenchymal arterioles and contributes to the increase in collateral circulation in cerebral occlusive disease like moyamoya disease. Vascular bypass surgery can reduce NO metabolites together with abnormal collateral circulation.