To evaluate the role of the autonomic nervous system in the regulation of atrial natriuretic peptide (ANP) secretion, the secretory responses of isolated perfused rat hearts to adrenaline and acetylcholine were studied. Infusion of adrenaline produced a dose-dependent rise in heart rate and contractile force associated with a marked increase in perfusate ANP immunoreactivity. The ANP response was almost completely abolished by the alpha-adrenoceptor antagonist phentolamine (10(-6)) and attenuated by the beta-adrenoceptor antagonist metoprolol (10(-5)). Thus, both alpha- and beta-adrenoceptors may mediate the adrenaline effect on ANP release. Perfusion of the isolated heart with 10(-6) or 10(-5) acetylcholine resulted in a short rise in hormone release followed by a gradual decline. The negative ionotropic and chronotropic effects of acetylcholine and the rise in ANP induced by acetylcholine were blocked by atropine, suggesting that a muscarinic receptor is involved. The finding that both adrenaline and acetylcholine alter ANP secretion rate points to the participation of autonomic nerves in the regulation of ANP release from atrial cardiocytes.