Human atrial natriuretic peptide (hANP) is a vasodepressor and a natriuretic hormone. The levels of plasma hANP increase during extracellular volume expansion. In the present study, we investigated whether plasma levels of hANP were associated with the severity of congestive heart failure (CHF), and whether such an association could be used as a diagnostic aid. Plasma hANP levels in 102 patients with various heart diseases and correlation between the plasma hANP levels and the left ventricular ejection fraction (EF) determined from echocardiography in 43 patients were examined. The plasma levels of hANP were high during the state of extracellular fluid overloading and atrial distention as determined by high right atrial pressure and pulmonary capillary wedge pressure. The high plasma hANP levels decreased in CHF patients whose clinical state improved, but remained high in those patients who were refractory to treatment. Plasma hANP levels correlated inversely with left ventricular EF (r = -0.41, p less than 0.01). In 9 patients reexamined during the course of treatment the plasma hANP levels decreased with an increase in EF. These data indicate that the level of plasma hANP is a practical diagnostic indicator of the severity of CHF, and can also be used as a means for assessing the efficacy of the treatment.