Radiolabeled alpha 2-antiplasmin cleared slowly from the circulation of mice. Complex formation with either plasmin or trypsin resulted in a significant increase in the plasma elimination rate of the protease inhibitor. Approximately 20 min and 14 min were required for 50% of the injected alpha 2-antiplasmin-plasmin and alpha 2-antiplasmin-trypsin to clear from the circulation, respectively. Significant competition was observed when radiolabeled alpha 2-antiplasmin-plasmin was cleared in the presence of a large molar excess of unlabeled alpha 2-antiplasmin-plasmin. alpha 1-Antitrypsin-trypsin failed to complete with radiolabeled alpha 2-antiplasmin-plasmin even when present at 2000 fold molar excess. Organ distribution studies localized the major site of alpha 2-antiplasmin-plasmin clearance in the liver. Microscopic autoradiography data suggested that the cell responsible for the clearance pathway was the hepatocyte.