In coronary artery ligated conscious dogs, intravenous (i.v.) injection of both morphine (8.0 mg/kg) and pethidine (12.0 and 24.0 mg/kg) inhibited the cardiac arrhythmia while naloxone (1.0 mg/kg) facilitated it. Intravenous pretreatment with naloxone completely blocked the morphine induced inhibition of the arrhythmia. Pethidine, however, elicited significant inhibition of the arrhythmia in the naloxone pretreated animals but its duration of action was markedly reduced. The temporal effect of i.v. injection of xylocaine (24.0 mg/kg) was parallel to that of pethidine (24.0 mg/kg) injected i.v. in the naloxone pretreated animals. In cervical spinal cord transected and bilaterally vagotomized dogs, i.v. injection of only 50.0 micrograms/kg of morphine elicited significant inhibition of the arrhythmia which was completely blocked by intrathecal pretreatment with a small dose (1.0 micrograms/kg) of naloxone. The same dose of naloxone, when given intravenously, failed to block the effect of morphine. The antiarrhythmic activity of morphine against the cardiac arrhythmia induced by coronary artery ligation appears to be due to activation of spinal opioid receptors. The local anaesthetic activity of pethidine contributes towards its early phase of antiarrhythmic activity.