In an attempt to determine factors that are related to atrial natriuretic factor (ANF) release in normal subjects, 10 male volunteers were studied at rest supine, sitting and during treadmill exercise. Echocardiography was used to measure atrial volumes, and a Swan-Ganz catheter was used to measure right atrial pressure and pulmonary artery wedge pressure. Right ventricular ANF increased from 33 ± 22 pg/ml supine to 72 ± 32 pg/ml at peak exercise (p < 0.001). When heart rate, atrial volume and atrial phasic pressure were combined to calculate atrial minute circumferential wall stress, a significant relationship between left and right atrial values for this variable and ANF was present. An association between norepinephrine (NE) and ANF was also present, but in a multivariate analysis it was not significant. This probably does not represent cause and effect but rather an association due to the relationship between NE and heart rate.