Although anticardiolipin antibody (aCL) has been suggested to be a potent risk factor for thrombosis and atherosclerosis in multiple arterial beds, conflicting results exist between aCL and cerebral ischemia in the general stroke population. To elucidate if this discrepancy relates to the heterogeneity of underlying etiologies, the blood beta(2)-glycoprotein I dependent-aCL in 432 Taiwanese adults was examined. The associated cerebral ischemia in these patients was classified into five subtypes according to the cause of cerebral ischemia. The results were compared with those in 100 healthy controls. A definite increase of aCL-IgG isotype was found in 41 patients (9.35%) and four controls (4.0%). The relative risk was 2.52. The frequency of increased aCL-IgG was 12.2%, 12.8%, 8.8%, 3.9%, and 3.5% in patients with large-artery atherosclerotic disease, stroke of unknown etiology, small-artery occlusive disease, cardioembolism, and stroke of other known etiology, respectively. Only patients with large-artery atherosclerotic disease (p<0.025) and stroke of unknown etiology (p<0.05) had higher frequencies of increased aCL than those in control subjects. The frequencies of abnormal results of activated partial thromboplastin time, antinuclear factor, Coombs' test, and venereal disease research laboratory were 2.84%, 1.22%, 1.02%, and 1.34% in these 41 patients, respectively. Accordingly, aCL-IgG selectively increases in patients with large-artery atherosclerosis and stroke of unknown etiology, reflecting selective activation of humoral immunity for aCL in the pathogenesis of cerebral ischemia.