Using isolated rat livers, Mattii et al. (Proc. Soc. Exper. Biol. Med. 116, 69, 1964) and Olson et al. (J. Clin. Invest 45, 690, 1966) observed generation of modest amounts of factor V. With rabbit liver-spleen combinations, Dodds and Hoyer (Br. J. Haem. 26, 497, 1974) found factor VIII emerging. We have perfused rat livers with rat blood cells in bovine albumin-Tyrode’s solution. One-stage assays for factors V, VIII, XI and XII indicated release of all 4 clotting activities within the first hour of perfusion, followed by a slow diminution. However, the same occurred if there were no liver in the perfusion system. When the rath erythrocytes were free of platelets (> 90%) and leukocytes (> 75%) before mixing with albumin-Tyrode’s, the isolated liver generated factor XII but not factors V, VIII and XI. Production of fibrinogen, prothrombin and factors VII, IX and X was not altered by removing the leukocytes and platelets.