The inhibitory effect of cardiac sympathetic nerve stimulation (SNS) on bradycardic response to vagal nerve stimulation was examined in anesthetized dogs pretreated with atenolol or propranolol to prevent tachycardia caused by SNS or norepinephrine infusion. The amplitudes of vagal bradycardia (0.5, 1, 2, and 4 Hz) during 10 and 30 Hz of SNS were significantly smaller than those during the resting state. The inhibitory effect of 10 Hz of SNS was neither affected by prazosin (10, 30 and 100 micrograms/kg i.v.) nor by yohimbine (10, 30 and 100 micrograms/kg i.v.). The SNS-induced inhibition of vagal bradycardia was inhibited by naloxone (0.3 and 1 mg/kg i.v.) or by naltrexone (0.3 and 1 mg/kg i.v.). Vagal bradycardia was unaffected by intracoronary infusion of norepinephrine (3 micrograms/min) into the right coronary artery, whereas it was effectively inhibited by leu-enkephalin (10, 30 and 100 micrograms/kg i.v.). Bradycardia induced by intracoronary injection of methacholine (0.3, 1 and 3 micrograms) was unaffected by SNS. These results suggest that a presynaptic alpha adrenoceptor mechanism is not involved in the SNS-induced inhibition of vagal bradycardia in the dog, and suggest further that an opioid receptor mechanism may be responsible for the inhibition.