To study the relationship between plasma alpha-atrial natriuretic peptide (alpha-ANP) and cardiac function in patients with Duchenne's progressive muscular dystrophy (DMD), we measured plasma alpha-ANP levels in 51 patients with DMD and evaluated them according to the clinical severity of the disease and the echocardiographic left ventricular function. In many of the patients with DMD, plasma alpha-ANP levels were mildly elevated, but no clear correlation was observed between alpha-ANP levels and wall motion abnormalities of the left ventricle. The alpha-ANP level was moderately or markedly elevated (81 to 120 pg/ml) in 3 of the 16 patients with respiratory failure and extremely high (1208 pg/ml) in the one patient with congestive heart failure. Two patients with respiratory failure and one with congestive heart failure, in whom alpha-ANP levels were elevated, died within 2 months. Elevation of left atrial pressure as a result of left ventricular dysfunction caused by impairment of the myocardium and elevation of right atrial pressure as a result of pulmonary hypertension caused by impairment of the respiratory muscles are considered to be involved in the mechanism of increased plasma alpha-ANP levels in patients with DMD. It can be concluded that a moderate or marked elevation in plasma alpha-ANP levels in patients with terminal DMD is a sign of a poor prognosis and may be a useful index for the management of the disease.