Protein C (PC) is considered to be an important regulator of blood coagulation and fibrinolysis. During the production of monoclonal antibodies (MoAbs) against human PC in mouse ascitic fluid, one hybridoma was found to induce heavy thrombus in mice, resulting in severe hemorrhage. Intravenous infusion of the purified MoAb (PC01) from this hybridoma also caused thrombosis in mice. The crossreacting substance was then isolated from mouse plasma with PC01 immunoaffinity column, which was identified as mouse PC by several criteria. Mouse PC prolonged the activated partial thromboplastin time of mouse plasma, and PC01 neutralized this in vitro anti-coagulant activity. Therefore, heavy thrombosis observed in PC01-treated mice is likely to be ascribed to the defect of PC caused by PC01.