The arrhythmogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham-operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site. The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation. Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias.