The effect of increased cholinergic activity on reperfusion induced ventricular arrhythmias was studied in alpha chloralose anaesthetised dogs by administering neostigmine during a 25 min occlusion of the anterior left descending coronary artery. The dogs were divided into five groups, each of 10 animals: the control group received only saline solution; group 1 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion (that is, 5 min before reperfusion); group 2 atropine 0.4 mg.kg-1 iv at 10 min of coronary occlusion and neostigmine 0.03 mg.kg-1 iv at 20 min; and group 3 neostigmine 0.03 mg.kg-1 iv at 20 min of coronary occlusion and at the same time underwent atrial pacing at the same rate as that of the sinus node just before neostigmine administration. In group 4 heart rate was slowed (junctional rhythm) by destroying the sinus node at 20 min of coronary occlusion. The results obtained showed that ventricular tachycardia and fibrillation, which occur at the beginning of reperfusion, were significantly less frequent in group 1 (p less than 0.001) and in group 4 (p less than 0.001). The protective action of neostigmine was abolished by previous administration of atropine (group 2) and modified by preventing the decrease in the heart rate by atrial pacing (group 3). In group 3 ventricular tachycardia was more frequent but the incidence of ventricular fibrillation was reduced significantly compared with the control and atropine groups. Thus cholinergic activity has a protective role in reperfusion arrhythmias by decreasing the heart rate before release of the coronary occlusion and therefore reduces the incidence of ventricular fibrillation.