Endotoxin-induced tumor necrosis has been shown to be mediated by a factor termed tumor necrosis factor (TNF). The biochemical nature, source, and mode of induction of TNF have been clarified. TNF is a mediator of activated macrophages that is released into the supernatant by these cells after their stimulation with endotoxin. A number of biologic functions of TNF other than its tumoricidal activity have been demonstrated. In vivo, TNF induces reactions similar to those induced by endotoxin. Hypothermia, elevated hematocrit and plasma lactate levels, and reduced plasma glucose levels have been measured in mice injected with TNF. These reactions typically occur soon after endotoxin injection and are induced with purified recombinant TNF in mice that exhibit a low response to endotoxin. No TNF-induced production of interleukin 1 (which can induce similar effects) was detected in macrophage/monocyte cultures. Therefore, TNF appears to mediate endotoxin effects directly.