Plasma levels of endothelin-1 are elevated in acute myocardial infarction with higher levels in complicated infarctions. Measurements of levels in unstable angina could help clarify whether the elevation is the consequence of cell necrosis or is in some way related to the pathophysiology of acute coronary syndromes. Plasma endothelin-1 levels were determined by radioimmunoassay in 29 patients with unstable angina and 6 with a myocardial infarction. Blood samples were obtained at admission before drug administration and 6 and 72 h later. Levels were also determined in 27 control subjects and in 29 patients with stable angina. Admission levels were similar in unstable angina, 0.635 +/- 0.052 pg/ml [log(1 + x)], and myocardial infarction, 0.746 +/- 0.122, and significantly higher than in controls, 0.428 +/- 0.047, and stable angina patients, 0.449 +/- 0.052 (p < 0.01). In unstable angina, levels decreased progressively to normal at 6 h, 0.557 +/- 0.049 pg/ml, and 72 h 0.474 +/- 0.054, as opposed to an increase to 0.868 +/- 0.109 (p < 0.05) after 6 h in myocardial infarction followed by a decrease to 0.597 +/- 0.122 at 72 h. The elevation in unstable angina did not correlate with other clinical or laboratory characteristics. Unstable angina is associated with an increase in endothelin-1 plasma levels during the acute phase, suggesting a role of this endothelium-derived vasoactive peptide in the pathophysiology of acute coronary artery syndromes.