Severe progressive failure of multiple organ systems has emerged during the past three decades as a common cause of death among patients in intensive care units. Sepsis is now better defined as systemic inflammatory response syndrome (SIRS), but its mortality rate has not changed and it continues to be a major health problem. Endotoxin interacts with plasma proteins and contributes to the pathophysiology of SIRS. Information is limited on the effect of endotoxin on human coagulation and fibrinolytic proteins in vivo, as well as on the cell response involved in the cytokine cascade. For this reason we performed quantitative assays to establish the sequence of events that occurs in vivo in the regulation of the contact and fibrinolytic pathways as well as in the cytokine cascade as a response to a single dose administration of endotoxin to normal non-smoking human volunteers.