Carswell et al. (1975) found a tumour necrosis factor (TNF) in the serum of endotoxin lipopolysaccharide (LPS)-treated animals primed with Bacillus Calmette Guerin (BCG), but LPS has strong undesirable side effects due to high toxicity and pyrogenicity. Lipoteichoic acid (LTA) from gram-positive bacteria has some immunological and biological activities in common with LPS but is only weakly pyrogenic and toxic. We investigated whether LTA can substitute for LPS in eliciting TNF. We administered LTA to mice primed with Propionibacterium acnes and found that the serum induced TNF. This serum caused a haemorrhagic necrosis of pre-established Meth-A fibrosarcoma in vivo and had an extensive cytotoxic effect on L-929 cells in vitro. Compared with LPS, LTA was much less toxic: no signs of toxicity were observed in LTA-treated mice, either normal or P. acnes-primed. The results suggest that LTA can induce TNF with low toxicity and may be a potential substitute for LPS in TNF induction.