Changes in glial cells were investigated immunohistochemically in the autopsy brains of patients with Binswanger-type infarction and the brains of rats with chronic cerebral hypoperfusion. Activated microglia, which are positive for MHC class II antigen, and GFAP immunoreactive astroglia were 3.1 times and 1.6 times, respectively, more numerous, in Binswanger-type infarction than in normal white matter. Chronic cerebral hypoperfusion after bilateral permanent occlusion of the carotid arteries elicited marked activation of microglia and an increase in astroglia in the medical corpus callosum after 1 day of occlusion, and these findings persisted up to 30 days after the occlusion. A decreased number of transferrin-immunoreactive oligodendroglia and rarefaction of the white matter were noted after 14 days of occlusion. These findings indicate that chronic mild ischemia may lead to rarefaction of the white matter, and that the activation of glial cells, which precedes rarefaction of the white matter, may be involved in the pathogenesis of Binswanger-type infarction.