Coagulation mechanisms were examined in the dog after a 70% hepatectomy and the additional effect of varying periods of ischemia on the liver remnant. Dogs were submitted to a 70% partial hepatectomy, and the liver remnant was rendered ischemic by occluding the vascular inflow. Dogs in the control group, those undergoing hepatectomy alone and those undergoing hepatectomy together with 60 min of ischemia time exhibited a fall in Hb and hematocrit values, a transient leukocytosis, a small increase in kaolin-cephalin clotting time and a decline in platelet count but no significant thrombocytopenia. Prothrombin time was changed in dogs undergoing hepatectomy, but this was not affected by ischemia. The characteristic rise in plasma fibrinogen postoperatively was abolished, and fibrinogen levels were lower in dogs undergoing hepatectomy alone and fell significantly in dogs subjected to 30-60 min of ischemia of the liver remnant. Factors V and VII were decreased after hepatectomy, and Factor V was more severely reduced after 30-60 min of ischemia. There was no overt bleeding tendency. In 10 dogs the liver remnant was subjected to ischemia for 75 min. Four of these died within 3 days of operation, 2 with severe hypoglycemia and 2 with postoperative bleeding. All 6 surviving dogs exhibited gross coagulation defects. Prothrombin time rose, kaolin-cephalin clotting time increased and platelets fell to a greater degree than in any of the other dogs. Plasma fibrinogen level showed a profound fall, as did Factor V, the magnitude of these changes being greater than after a shorter period of ischemia. Factor VII was also decreased, but this did not appear to be related to the ischemic interval. In the clinical situation in which intrinsic coagulation mechanisms are impaired, treatment with Factor V and VII concentrates may be the best way of correcting the coagulation defect.