The administration of endotoxin to humans elicits a variety of acute inflammatory responses that are qualitatively similar to those that occur during the early stages of clinical sepsis. As a model of acute inflammation it provides a unique opportunity to evaluate the temporal response and interactions among the various mediators of this syndrome. Disorders of the hemostatic and the fibrinolytic systems are common in septic shock. These are manifested by the consumption of platelets and coagulation proteins, activation of the fibrinolytic system, and the development of microvascular thrombosis. 1 Deposition of fibrin aggregates and microthrombi in various organs is a common histologic finding in septic shock and contributes to the development of multiple organ dysfunction characteristic of this syndrome. 2 , 3 Knowledge of the mechanisms that lead to these abnormalities of hemostasis is important in the development of new therapies for septic shock. This chapter summarizes observations of changes in the fibrinolytic system in humans following endotoxin administration.