This review summarizes experiments on the endogenous induction of tumor necrosis factor (TNF) in mice by various biological response modifiers and bacterial preparations, such as heat-killed Streptococcus pyogenes (OK-432) or Lactobacillus casei (LC). Intravenous administration of OK-432 or LC transiently elicited endogenous TNF in mice. The endogenous TNF production was significantly enhanced by priming (pretreatment) with high molecular-weight lignins or polysaccharides, but not by phenylpropenoid precursors or partially hydrolyzed products of glucans. When stimulated with lignins and OK-432, tumor-bearing and aged mice produced much lower amounts of TNF than normal and young mice. Endogenously produced TNF was concentrated more in serum, liver and lungs, than in other organs. On the other hand, a much lower concentration of IL-1alpha was induced in the serum fraction, whereas significant amounts of this cytokine were detected in liver and lungs. Histochemical examination revealed significant increase in the number and swelling of Kupffer cells and sinusoidal endothelium in the liver of the treated mice. The results suggest the possible efficacy of applying endogenous TNF production for the treatment of human cancer patients.