It has been established that pretreatment with the selective mu-opioid receptor (OR) agonist DALDA (0.1 mg/kg, i.v.) or the selective delta1-OR agonists DPDPE (0.09 mg/kg) and/or (-)-TAN-67 (0.08 mg/kg) has no effect on the incidence of ventricular arrhythmias induced by a 10-min coronary artery occlusion and a 10-min reperfusion in ketamine-anesthetized rats. In contrast, the pretreatment with the selective delta2-OR agonist deltorphin II (0.12 mg/kg) and the proposed delta2-OR agonists deltorphin D (0.3 mg/kg) and/or dermorphin H (0.23 mg/kg) increases cardiac resistance to the arrhythmogenic action of acute ischemia and reperfusion. Administration of the mixed mu- and delta-OR agonist dalargin (0.12 mg/kg) 15 min before the coronary artery ligation abolished only the reperfusive ventricular fibrillation. It is concluded that peptidergic stimulation of delta2-ORs can be used as a new means of increasing cardiac tolerance to the arrhythmogenic effects of acute ischemia and reperfusion.