In a prospective study, 22 patients with prolonged chest pain were monitored by serial serum tumour necrosis factor-alpha (TNF; cachectin) measurements. In five patients serum TNF markedly increased, peaking at greater than 145 ng l-1; all these patients had large infarcts complicated by hypotension, pulmonary oedema and/or arrhythmia. Two of these patients died. In contrast, TNF levels were either normal or only slightly raised in patients with small or uncomplicated infarcts and in patients with prolonged angina without evidence of infarction. The results show that extensive myocardial infarction induces the release of the monocyte/macrophage-derived polypeptide hormone TNF into circulation. This finding may be clinically relevant with respect to systemic metabolic consequences of myocardial infarction.