Bacterial endotoxin, which is thought to be a direct cause of shock or tissue damage of multi-organs in Gram-negative septis, has been studied on their biological activities for a long time. In the last several years, the advance in endotoxin research has been very rapid. Macrophage activation is the first and essential step in the course of endotoxin action and is followed by the release of many kinds of mediators including cytokines such as tumor necrosis factor α (TNFα)/cachectin, interleukin-1 (IL-1), interleukin-6 (IL-6), interferons, and colony-stimulating factors, and lipid derivatives such as prostaglandines, leukotrienes, and platelet-activating factor. Of these mediators, TNF α/cachectin and IL-1 play a central role in the multiple activities of endotoxin. TNF α and IL-1 have many similar activities and exert alone or cooperatively the endotoxin-like activities such as lethal toxicity, pyrogenesis, promotion of coagulation and leukocyte adherence to endothelial cells, and induction of acute phase proteins. Endotoxin tolerance and Shwartzman reaction are also mediated through these inflammatory cytokines. On the basis of these findings, some remedies using anti-TNF α monoclonal antibody or antagonist of IL-1 are under research for septic shock as well as clinical use of TNF α for cancer therapy.