The effects of alpha- and beta-adrenergic stimulation on release of atrial natriuretic factor (ANF) were examined in seven anesthetized, open-chest pigs. The alpha-adrenergic agonist phenylephrine (28.0 micrograms/min) and the beta-adrenergic agonist isoproterenol (0.3 micrograms/min) were infused into the proximal part of the circumflex coronary artery to stimulate the left atrial adrenoceptors without concomitant changes in left and right atrial filling pressures (v wave). Isoproterenol reduced plasma immunoreactive ANF (irANF) by 15 +/- 7 pg/ml (20%) from 76 +/- 10 pg/ml despite a rise in left atrial systolic pressure (a wave). A comparable rise in left atrial systolic pressure, induced by intracoronary infusion of calcium chloride (8.0 mg/min), increased plasma irANF by 33 +/- 10 pg/ml (53%) from 62 +/- 7 pg/ml. Phenylephrine increased plasma irANF by 9 +/- 4 pg/ml (14%) from 66 +/- 10 pg/ml without altering right and left atrial pressures. A rise in left atrial filling pressure of 3.2 +/- 0.5 mm Hg, induced by constricting the ascending aorta, increased plasma irANF by 83 +/- 35 pg/ml (141%) from 59 +/- 11 pg/ml. This increase was nine times that during phenylephrine infusion. In conclusion, alpha-adrenergic stimulation increases and beta-adrenergic stimulation inhibits ANF release by a direct action on the atrial myocytes. The direct effects of alpha- and beta-adrenergic stimulation on ANF release in vivo are small compared with the effect of a moderate rise in atrial filling pressure.