To examine the sites of release and removal of plasma atrial natriuretic polypeptide plasma levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were measured in 11 control subjects and 22 patients with mitral stenosis. Mean plasma natriuretic polypeptide levels in the femoral vein, right atrium, pulmonary artery, pulmonary capillary bed, left atrium and aortic root were, respectively, 64 +/- 29, 124 +/- 72, 103 +/- 44, 83 +/- 30, 106 +/- 46 and 101 +/- 35 pg/ml in the control subjects and 321 +/- 170, 500 +/- 234, 458 +/- 266, 356 +/- 209, 434 +/- 222 and 432 +/- 217 pg/ml in the patients with mitral stenosis. In both the control subjects and the patients with mitral stenosis, there was a significant increase between the femoral vein and the right atrium and between the pulmonary capillary bed and the left atrium and a significant decrease between the pulmonary artery and the pulmonary capillary bed. Blood samples were also taken simultaneously from the pulmonary vein and the pulmonary capillary bed, as well as from the pulmonary artery and the left atrium, in 25 patients (11 control subjects, 5 patients with mitral stenosis and 9 patients with atrial septal defect). There was no difference in plasma atrial natriuretic polypeptide levels between the pulmonary capillary bed and the pulmonary vein in these 25 patients. It is concluded that atrial natriuretic polypeptide 1) is released into the left as well as the right atrium, and 2) is removed by the lungs.