Adrenomedullin is a potent vasodilator and natriuretic peptide that may an important role in cardiovascular disease. To investigate the role of adrenomedullin in the pathophysiology of congestive heart disease, plasma levels of adrenomedullin were measured in patients with congestive heart failure. Venous blood samples at rest were obtained before and after treatment from patients with congestive heart failure in New York Heart Association functional class II (n-23), III (n-26) and IV (n-14) and from normal subjects (n-30). Plasma adrenomedullin, endothelin-1,2, and atrial natriuretic peptide were determined by radioimmunoassay, plasma noradrenaline by radioenzymatic assay. Left ventricular ejection fraction was measured by echocardiography. The mean plasma level of adrenomedullin in normal subjects was 8.2 pmol/l, tended to be increased in patients with congestive heart failure those in class II (12.9 pmol/l) and were significantly increased in classes III and IV (21.3 and 29.9 respectively). Plasma adrenomedullin was correlated strongly with endothelin-1,2, atrial natriuretic peptide, and noradrenaline, and relatively weakly with left ventricular ejection fraction. Plasma adrenomedullin levels significantly decreased after treatment. These findings indicate that plasma levels of adrenomedullin are elevated in congestive heart failure and may be involved in the defense mechanism against further peripheral vascular resistance elevation in congestive heart failure.