To evaluate the relationship between plasma atrial natriuretic polypeptide (ANP), hemodynamic parameters, and plasma catecholamines and, in addition, to determine whether circulating ANP is metabolized in the pulmonary circulation, plasma concentrations of ANP were determined in 40 patients with chronic left-sided heart failure. After at least 30 minutes of bed rest with the patient in the supine position, blood samples were drawn simultaneously from both the main pulmonary artery (mPA) and the ascending aorta (Ao) before administration of contrast medium. The plasma ANP concentrations significantly decreased from the mPA to the Ao (135.3 +/- 18.1 pg/ml vs 127.4 +/- 19.4 pg/ml; mean +/- SEM, p less than 0.05). The plasma ANP level in the mPA correlated with the plasma norepinephrine level in the Ao (r = 0.71, p less than 0.01), right atrial pressure (r = 0.34, p less than 0.05), mean pulmonary capillary wedge pressure (r = 0.829, p less than 0.001), and left ventricular end-diastolic pressure (LVEDP) (r = 0.88, p less than 0.001). Of the various hemodynamic parameters and plasma catecholamine concentrations in the Ao, only LVEDP was found to be an independent and significant predictor of plasma ANP levels in the mPA. These results indicate that ANP released from the heart is regulated mainly by preload (LVEDP) in cases of left-sided heart failure and that circulating ANP is metabolized in the pulmonary circulation. In conclusion, the plasma ANP concentration may be a useful noninvasive index of LVEDP in patients with chronic left-sided heart failure.