We have established a system for etiological analysis of thrombophilia which includes assays of antithrombin III, protein C, protein S, plasminogen, fibrinogen, heparin cofactor II and lupus anticoagulants as well as gene analysis. The analysis conducted on 115 patients with venous thrombosis, arterial thrombosis and small vessel thrombosis revealed that forty-one patients(36% of the examined patients) were accompanied with decreased activities of protein S, protein C, antithrombin III and plasminogen. Eleven candidate causal mutations were found by gene analysis. These studies indicate that a comprehensive examination is instrumental in identifying and confirming the etiology in patients with thrombophilia.