There is increasing evidence that gram-negative bacteria via endotoxin induce the excessive production of inflammatory cytokines, which are active in the pathogenesis of septic shock, multiorgan failure, and ARDS. In animals the injection of TNF induces pathophysiologic and histopathologic changes that are characteristic of the septic shock syndrome, and in patients there is a close association between levels of TNF and the severity of the shock. IL-1 and IFN-gamma markedly potentiate the toxic TNF effects in animal experiments. IL-6 is frequently released into serum during septic shock, and its levels are associated with the severity of the shock. The cytokine is probably not directly involved in the pathogenesis of the shock but may contribute to fever, neutrophilia, and production of acute-phase proteins. Endothelial cells and neutrophils are important target cells for the cytokines in mediation of septic shock and late complications. Underlying conditions like cancer, trauma, burns, and other kinds of stress may alter the induction mechanism of the cytokines and the susceptibility of the organism. The pathogenetic significance of TNF and other cytokines in different categories of septic shock remains to be clarified.