White matter changes, which are noted in Binswanger's disease and which may be due to ischemia, have previously been explained mainly on the basis of the hemodynamic mechanism. To elucidate the etiopathophysiology of Binswanger's disease from the hemorheology viewpoint, platelet activation in the cerebral circulation was studied in 30 patients with Binswanger's disease, who satisfied the diagnostic criteria of Binswanger's disease proposed by Bennett et al. Plasma beta-thromboglobulin concentration gradients (delta BTG) between the jugular vein and the antecubital vein, as indicators of platelet activation in the cerebral circulation, were determined in these patients (Binswanger's disease group) compared with those of different stroke subtypes groups (lacunar, atherothrombotic, cardioembolic) in the chronic phase and 25 patients with various diseases other than stroke (non-stroke group). Among these groups, the elevation of delta BTG levels in the Binswanger's disease group (4.55 +/- 6.95) were so frequent and prominent that differences were significant, especially in comparison to those of the cardioembolic group, and the non-stroke group. The enhanced platelet activation in the cerebral circulation observed in Binswanger's disease indicated not only the widespread development of underlying vascular lesions, but also accelerated release reaction of vasoactive substances from platelets into the blood stream, which could biochemically injure the vascular wall and neurons downstream, resulting in Binswanger's disease.