In fulminant hepatic failure disturbances of blood coagulation are caused by both delayed synthesis and increased consumption of hemostatic proteins. The enhanced turnover of clotting factors and inhibitors may be induced by thrombin and plasmin after activation of the coagulation system by thromboplastic material and activators of plasminogen released from necrotic liver cells. Additionally, proteases such as elastase released from granulocytes, may be involved when infectious complications occur. The immunologic determination of the specific proteinase-inhibitor complexes thrombin-antithrombin III, plasmin-alpha 2 antiplasmin, and elastase-alpha 1 antitrypsin is of great diagnostic value to verify and differentiate the proteolysis of hemostatic proteins. Five patients with FHF were treated with plasma derivatives (FFP and AT III concentrates) until the liver had recovered and resumed synthesis of clotting factors and their inhibitors. The coagulation parameters normalized, bleeding complications and microcirculatory failure could be prevented. The data suggest that a comprehensive substitution of plasma components improves considerably the prognosis of acute liver failure.