Activated protein-C (APC) resistance, a poor anticoagulant response to APC due to a mutation of the factor V gene (factor V Leiden, FVL), has recently been reported to be the most common hereditary coagulation disorder associated with familial deep venous thrombosis. However, all data have been derived from investigation of Western populations. Therefore we investigated the prevalence of low APC ratios (APC resistance) and FVL in Japanese patients suffering from ischemic stroke (n = 106) and neurological diseases without vascular involvement (n = 37). We conclude that the prevalence of low APC ratios (APC resistance) and FVL is very low in Japanese ischemic stroke patients, and the low APC ratio found in 2 of 143 subjects might be attributable to coexistent antiphospholipid antibodies and/or protein-S deficiency rather than to FVL. Our results suggest the existence of racial differences in the frequency and cause of APC resistance.