To study the relationship between the plasma concentration of the atrial natriuretic peptide (ANP) and heart function and to discern the secretion pathway of ANP, we determined the peripheral plasma concentration of ANP in 18 heart patients and the intracardiac concentration of ANP in six heart patients during cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge by acid alcohol. The concentration of ANP was determined by a sensitive and specific radioimmunoassay method. We found that the plasma ANP concentration (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was statistically higher than that in normal adults (ranging from 8 to 20, mean = 12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was inversely correlated with the left ventricular ejection fraction (r = -0.53, p less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107 +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is mainly secreted via the coronary sinus into the atrial cavity. The peripheral plasma ANP concentration is higher in heart patients. It increases as the left ventricular ejection fraction decreases. Therefore, plasma ANP concentration may be a useful indicator for the assessment of cardiac function.