The study by Carswell et al. investigates the mechanism of "hemorrhagic necrosis" of tumors induced by endotoxin. They found that the serum of bacillus Calmette-Guérin (BCG)-infected mice treated with endotoxin contains a substance called tumor necrosis factor (TNF), which enhances tumor necrosis. TNF is not residual endotoxin but a factor released from host cells, likely macrophages, by endotoxin. Corynebacteria and Zymosan, which induce hyperplasia of the reticulo-endothelial system, can also prime mice for TNF release by endotoxin. TNF is toxic to two neoplastic cell lines in vitro but not to mouse embryo cultures. The authors propose that TNF mediates endotoxin-induced tumor necrosis and may be responsible for the suppression of transformed cells by activated macrophages. The study also explores the optimal conditions for TNF production and its activity in different tumor models and mammalian species.The study by Carswell et al. investigates the mechanism of "hemorrhagic necrosis" of tumors induced by endotoxin. They found that the serum of bacillus Calmette-Guérin (BCG)-infected mice treated with endotoxin contains a substance called tumor necrosis factor (TNF), which enhances tumor necrosis. TNF is not residual endotoxin but a factor released from host cells, likely macrophages, by endotoxin. Corynebacteria and Zymosan, which induce hyperplasia of the reticulo-endothelial system, can also prime mice for TNF release by endotoxin. TNF is toxic to two neoplastic cell lines in vitro but not to mouse embryo cultures. The authors propose that TNF mediates endotoxin-induced tumor necrosis and may be responsible for the suppression of transformed cells by activated macrophages. The study also explores the optimal conditions for TNF production and its activity in different tumor models and mammalian species.