Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with organic heart disease undergoing diagnostic cardiac catheterization. Independent of nature and duration of the disease (valvular heart disease, congestive cardiomyopathy) plasma ANP levels were closely related to the severity of cardiac failure. Furthermore, plasma ANP levels were found to be negatively correlated with the cardiac index and to be positively correlated with right and/or left atrial and with pulmonary artery pressures. During physical exercise (bicycle ergometer) a marked increase of plasma ANP levels was observed, which was closely related to increments in mean pulmonary artery pressure. This rise in plasma ANP levels during physical exercise was not attenuated in patients with already elevated resting plasma concentrations of ANP. In patients with congestive cardiomyopathy, afterload-reduction by ACE-inhibition resulted in changes of central hemodynamics, which were closely reflected by venous concentrations of ANP. The measurement of plasma ANP levels may serve as an indicator of the severity of cardiac failure. Plasma concentrations of ANP, however, are neither helpful in establishing the etiology of the underlying heart disease nor in differentiating left and right heart failure. However, in cases of already established organic heart disease plasma ANP levels may be used as a marker for assessing the efficacy of the therapeutic regimen.