Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, the current study was performed to test the hypothesis that plasma endothelin concentrations are elevated in patients with chronic congestive heart failure. Plasma levels of endothelin were measured with sensitive and specific radioimmunoassay. Venous blood samples were obtained after 60 minutes of supine rest and serially during 40 minutes in the upright position. It was found that patients with congestive heart failure had markedly higher basal levels of circulating endothelin than subjects with coronary heart disease without heart failure and there was no further increase on postural change. Increase in plasma endothelin during upright position in subjects with coronary heart disease without heart failure, preceded the increases in circulating levels of the other vasoconstrictor mediators, consistent with the role of endothelin in neurohumoral compensation for hemodynamic stress.