Blood coagulation equilibrium in the hepatic sinusoids may be deranged after orthotopic liver transplantation, since tissue factor activity increases in Kupffer cells and thrombomodulin expression disappears in sinusoidal endothelial cells in orthotopically transplanted rat liver. The presence of sinusoidal blood coagulopathy and its contribution to the development of early graft failure following orthotopic liver transplantation were investigated in rats. Orthotopic liver transplantation was performed using livers preserved in cold UW solution, according to the method of Kamada, in rats. Abnormalities in the hepatic sinusoids were evaluated electron-microscopically. Anticoagulation therapy was done using antithrombin III concentrate infused immediately and 12 hr after operation. Fibrin deposition and endothelial cell destruction in the hepatic sinusoids were observed in transplanted rats 5 hr after operation. In these rats, plasma antithrombin III activity was decreased to less than 40%o of normal levels, and massive hepatic necrosis developed with increased plasma thrombin-antithrombin III complex concentration 24 hr after operation. Anticoagulation therapy significantly attenuated the extent of hepatic necrosis, with normalization of plasma antithrombin III activity and further increase in plasma thrombin-antithrombin III complex concentration. A hypercoagulative state exists after orthotopic liver transplantation in rats. Fibrin deposition in the hepatic sinusoids associated with this state may contribute to the development of early graft injury.