These studies were undertaken to determine the type and availability of the procoagulant activities generated in blood incubated with endotoxin. The shortening of the recalcification time of blood incubated with endotoxin was directly correlated with the increase in synthesis of tissue thromboplastin in the monocytes. The procoagulant activity which resulted in the shortening of the clotting time was shown to be almost totally blocked by tissue thromboplastin antibodies. Thus, no additional procoagulant activity was generated in platelets during the 5 h incubation of blood with endotoxin. However, lysed platelets enhanced the synthesis of tissue thromboplastin in blood monocytes in the presence of endotoxin. Lysed red blood cells or granulocytes had no such effect. In endotoxin stimulated monocytes the main part of the newly synthesized tissue thromboplastin appeared to be exposed on the cellular surface. Thus, only 25% of the tissue thromboplastin activity was recovered when tissue thromboplastin antibodies had been present during the stimulation. Unstimulated monocytes were also found to possess tissue thromboplastin activity, but this low activity was not affected by tissue thromboplastin antibodies unless the monocytes were disrupted by sonication. The high percentage of tissue thromboplastin exposed on the surface of the endotoxin stimulated monocytes in whole blood may contribute significantly to the rapid induction of disseminated intravascular coagulation in gram negative sepsis.