The aim of the present study was to investigate the influence of moxonidine, a representative of I1-imidazoline-receptor agonist, on arrhythmias induced by myocardial ischemia or reperfusion. Acute myocardial infarction was produced by tightening a previously placed loose silk loop around the coronary artery in conscious rats. Moxonidine (0.01, 0.03, or 0.10 mg/kg i.v., 10 min before coronary ligation) significantly decreased the incidence of ventricular tachycardia during the first 15 min of infarction (70 versus 100% in controls), and the number of animals that survived without developing any arrhythmia was increased (15, 20, and 25%, respectively, versus 0%). Reperfusion-induced arrhythmias were produced by releasing a snare after 6 min of myocardial ischemia in anesthetized, artificially ventilated rats. Reperfusion rapidly induced severe dysrhythmias in all of the control animals. Moxonidine pretreatment (0.03 and 0.10 mg/kg) decreased the incidence of ventricular fibrillation (25 and 30% versus 64%) and increased the number of animals that survived without developing any arrhythmia (20 and 25% versus 0%). We conclude that moxonidine offers significant protection against the development of arrhythmias induced by acute regional myocardial ischemia in conscious rats. Moxonidine pretreatment also provides a beneficial effect during reperfusion-induced arrhythmias that appear after a brief period of myocardial ischemia.