To detect myocardial cell damage, serum samples of 42 consecutive patients with angina at rest were screened for cardiac myosin light chains, which were detected in 22 patients (52%). In 17 of these patients there was a persistent release of myosin light chains lasting until the 4th hospital day, whereas in 7 patients myosin light chains were only detectable during the initial 24 h after admission. The presence of myosin light chains correlated with signs of ischemia in the electrocardiogram (ECG) (p less than 0.05) and with the extent of coronary artery narrowing (p less than 0.05). Cardiac myosin light chains were elevated in serum only if there was a greater than or equal to 75% diameter narrowing in at least one major vessel. In all five patients who developed transmural myocardial infarction during the course of their hospital stay, myosin light chains were detectable greater than or equal to 28 h before the diagnosis of myocardial infarction could be established by ECG criteria and conventional serum enzymes. Thus the detection of circulating cardiac myosin light chains enables one to identify a subgroup of patients with angina at rest having more severe coronary artery disease with a worse outcome.