Tumor necrosis factor (TNF) has been determined as an endogenous mediator for endotoxin-induced tumor necrosis. This macrophage product has been biochemically characterized and its protein structure defined by molecular cloning of the TNF gene. Experiments with antibodies to TNF demonstrated that TNF acts as an effector molecule of activated cytotoxic macrophages involved in tumor destruction. Purified TNF has been shown to exert direct necrotic activity against tumors in vivo. In addition, a number of similar effects in vivo and in vitro of TNF, endotoxin, and interleukin 1 (IL 1) have been observed. For example, in vivo the thermoregulatory activity of TNF is similar to IL 1. Since TNF was found to mediate other effects of endotoxin in modulating immune responses in addition to the tumor necrotic activity, it can be considered a true immunoregulator produced by macrophages after endotoxin stimulation.