Endothelin (ET) is a recently discovered, endothelium-derived peptide that may be the most potent vasoconstrictor yet identified. Although there is much interest in the possible systemic actions of circulating ET in vivo, there is no data on ET levels under physiological conditions, or in cardiovascular disease. We used a radioimmunoassay that was sufficiently sensitive to detect ET immunoreactivity (irET) in the SepPak-extracted plasma from 14 healthy volunteers in a range from 0.03 to 0.69 pg/ml (mean 0.26 +/- 0.236 pg/ml). ET levels were not significantly different from normal in 5 patients with stable congestive heart failure (0.46 +/- 0.36 pg/ml). However, irET was increased markedly in 6 patients in cardiogenic shock (3.65 +/- 1.14 pg/ml), and (less so) in 6 patients on chronic dialysis (1.05 +/- 0.41) and in 4 with pulmonary hypertension (1.52 +/- 0.45) (p less than 0.001). The present results suggest that circulating irET concentration is responsive to altered cardiovascular conditions, and therefore support a potential role for ET as a vasoactive hormone.