To identify arterial changes that are characteristic of Binswanger's encephalopathy (BE), we analyzed cerebral subarachnoid and medullary arteries of seven BE autopsy specimens by reconstruction of stained serial sections. We also noted the frequency of intimal fibrosis with or without atheroma of the subarachnoid arteries, and determined the medial thickness of the subarachnoid and medullary arteries. The results for the BE specimens were compared with those of six hypertensive brain hemorrhage (HH) specimens and six normotensive (NT) specimens from patients without cerebral abnormalities. In medullary arteries of BE in comparison with HH, we observed nonspecific but significantly more widespread intimal fibrosis with or without atheroma, as well as segmental loss of the medial smooth muscle cells (SMCs), which was sometimes associated with intimal plasma exudation or microaneurysm. A few medullary arteries in BE were completely occluded by fibrous connective tissue. Intimal fibrosis of the subarachnoid arteries was significantly more widespread in BE than in HH and NT. The media of the subarachnoid and medullary arteries was significantly thicker in BE and HH than in NT, and tended to be thicker in BE than in HH. In NT specimens the medullary arteries tended to be thinner in medial thickness than the subarachnoid arteries. These findings suggest that dysfunction of blood flow regulation due to increased arterial stiffness caused by hypertension-induced intimal fibrosis and loss of medial SMCs is an essential mechanism resulting in diffuse myelin loss of the cerebral white matter in BE, whereas luminal stenosis or occlusion and adventitial fibrosis are secondary. Moreover, selective and severe involvement of the cerebral medullary arteries compared with the subarachnoid arteries may be explained by the following two factors, (1) that many medullary arteries have normally dilated segments, and (2) that their media is thinner compared with that of the subarachnoid arteries of the corresponding diameter.