Endotoxic reactions induced in mice by recombinant human tumor necrosis factor (TNF) were examined. Mice showed a dose-dependent hypothermia after intravenous TNF injection which was similar to a reaction to lipopolysaccharide injection. Plasma glucose levels were decreased, and plasma lactate levels were increased. Blood hematocrit levels were increased after TNF injection. No interleukin-1 activity was detected in the plasma of TNF-treated animals. The number of leukocytes was reduced 30 min after TNF injection and returned to normal within 24 h. Thus, the data demonstrate that the pathophysiological effects induced by TNF were similar to the effects induced by bacterial endotoxin. Since lipopolysaccharide is a very potent agent for eliciting TNF release from activated macrophages, these results suggest that TNF could act as an endogenous mediator of endotoxin effects.