Data have been presented suggesting that blood thromboplastin given intravenously to rats is cleared by the reticuloendothelial system. (1) The reagent given into the jugular vein or aorta caused profound defibrination, whereas injection into the portal circulation caused a milder reaction. These differences were obtained irrespective of the source of phosphatide in the thromboplastin generation mixture. (2) Reticuloendothelial blockade reduced the protective effect of portal administration. (3) Radioactive blood thromboplastin given intravenously was rapidly cleared from the blood, and showed an organ distribution resembling that of agents known to be removed by reticuloendothelial cells. (4) Injection of the blood thromboplastin during a carbon clearance caused depression of the carbon disappearance slope.