The activated protein C (APC)-resistance test is a simple and reliable method for detecting reduced sensitivity to the anticoagulant action of this protein. We investigated the sensitivity to APC in 180 Japanese controls and in 96 Japanese patients with venous and arterial thrombosis (28 with deep vein thrombosis; 13 with pulmonary thromboembolism; 41 with cerebral infarction; and 14 with coronary artery disease). All of the patient groups showed significantly reduced sensitivity to APC, reflected by the lower normalized APC-sensitivity ratio (n-APC-SR), as compared with healthy control. The APC-sensitivity ratio was negatively correlated with plasma activated factor VII levels. These results suggest that the low n-APC-SR is related to venous or arterial thrombotic disease. The APC resistance may serve as a potential marker for assessing the hypercoagulable state.