Reye's syndrome affects children with a history of viral infection treated with aspirin. Its pathogenesis is unclear. Tumour necrosis factor (TNF) is released by macrophages activated by viral infection, endotoxin, and phagocytosis, and it has been shown to be a mediator of the toxic and metabolic effects of endotoxaemia. The metabolic effects of endotoxin and TNF are similar to those found in Reye's syndrome. Raised levels of TNF are released from macrophages treated with non-steroidal anti-inflammatory drugs, and young animals are known to be more sensitive than mature animals to both TNF and endotoxin. These observations lead to the hypothesis that an increased release of TNF in selected young patients treated with aspirin contributes to the development of Reye's syndrome.