Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. We have shown previously that this "atrial natriuretic factor" may be released in vitro from incubated atria by muscarinic cholinergic stimulation. Experiments reported here demonstrate that incubation with adrenalin or arginine vasopressin, but not with deamino-8-D-arginine vasopressin, also results in liberation of atrial natriuretic factor. Since the effective agonists have in common activation of the cellular polyphosphoinositide system with consequent production of inositol triphosphate, we suggest that inositol triphosphate is the second messenger of stimulus-secretion coupling in atrial cells.