Atrial natriuretic factor, a peptide found in mammalian cardiac atria, has natriuretic and vasodilatory properties that may be important in the regulation of intravascular volume. To study factors related to its release in human subjects, intracardiac pressures and plasma atrial natriuretic factor concentrations in the central circulation were measured in 34 patients with a variety of cardiovascular disorders. Plasma atrial natriuretic factor concentration increased from the inferior vena cava to the right atrium (76 +/- 24 to 162 +/- 37 pg/ml, p less than 0.001) and from the vena cava to the aorta (76 +/- 24 to 177 +/- 46 pg/ml, p less than 0.001). Mean right atrial pressure was positively correlated with atrial natriuretic factor concentration in the pulmonary artery (r = 0.58, p less than 0.001), and mean pulmonary capillary wedge pressure was positively correlated with concentration in the aorta (r = 0.64, p less than 0.001). In six patients whose atrial natriuretic factor concentrations were measured at two different levels of atrial pressure, increased atrial pressure was accompanied by increased atrial natriuretic factor concentration in the pulmonary artery (p less than 0.01) and aorta (p less than 0.01). Atrial natriuretic factor levels measured in fresh myocardium from a patient undergoing cardiac transplantation showed tissue concentrations in the atria 500-fold higher than tissue concentrations in the ventricles. These data document that atrial natriuretic factor is found in human atrial myocardium and suggest that it may be released in response to increased atrial pressure. Such a secretory release mechanism is consistent with the hypothesis that atrial natriuretic factor plays a role in the regulation of circulatory volume.