The role of the liver in the regulation of fibrinolytic activity was investigated utilizing four different experimental situations. During liver transplantation fibrinolytic activity increased very significantly. However, from 2 to 24 hours postoperatively fibrinolytic activity was found to be significantly subnormal. It became normal in the second and third days. In the hepatectomized dog fibrinolytic activity increased more than three times within 30 minutes and then became normal in a few hours. Following partial devascularization of the liver, fibrinolytic activity initially increased moderately and then was maintained at subnormal levels for two days. When the liver was uniformly devascularized, fibrinolytic activity continuously increased until death. It appears that the presence of the liver is necessary to effect the compensatory decrease in fibrinolytic activity that takes place following ischemic injury to it.