The release of adrenal catecholamines into the adrenal vein elicited by splanchnic nerve stimulation, was evaluated in the presence of a beta-adrenoceptor agonist and both beta-1 and beta-2 adrenoceptor antagonists in anaesthetized and vagotomized dogs. Stimulations (0.5 V pulses of 2 ms duration for 3 min at 1 Hz) were applied before and after the i.v. infusion of the beta-adrenoceptor agonist, isoproterenol (0.1 microgram/kg/min). While maintaining the infusion of isoproterenol, either ICI 118551 (0.3 mg/kg), a selective beta-2 adrenoceptor antagonist, or 204-155 (0.2 mg/kg), a selective beta-1 adrenoceptor antagonist (Sandoz Co., Dorval, PQ, Canada), were injected intravenously and the stimulation was repeated. The results show that isoproterenol increased significantly both pre-stimulation basal levels and the stimulated release of catecholamines. These potentiated responses were significantly reversed by ICI 118551, but not by 204-155. These results suggest that the release of adrenal catecholamines is locally modulated by a positive feedback mechanism through activation of beta-2 adrenoceptors.