According to the current concept, anginal pain results from stimulation of sympathetic nerves within the heart. In this study, we evaluated the role of cardiac adrenergic denervation in exercise-induced angina pectoris in 15 men with recent acute myocardial infarction. Before discharge from the hospital, the patients were subjected to a symptom-limited exercise test. Three months after the infarction, cardiac scintigraphic studies using I-123 metaiodobenzylguanidine (MIBG), I-123 paraphenylpentadecanoic acid (pPPA), and Tc-99m sestamibi (MIBI) were performed in order to determine the extent of denervated myocardium, the size of infarction, and myocardium with reduced perfusion, respectively. MIBG defect (17.2 +/- 7.6% of left ventricular mass) (defect defined as an activity distribution < or = 30% of the maximal myocardial activity) was larger than pPPA defect (8.3 +/- 8.8%, p < 0.001) in all patients, which indicates that the area of myocardial necrosis was surrounded by viable myocardium with sympathetic denervation. The extent of viable but denervated myocardium was significantly greater in patients who developed angina pectoris than in patients without angina pectoris during the early exercise test (13.3 +/- 4.4% vs 5.0 +/- 2.4%, p < 0.001). In addition, patients with silent ischemia tended to have smaller areas of viable but denervated myocardium than patients with painful ischemia (5.7 +/- 3.8% vs 13.8 +/- 5.1%, p = 0.07). Thus, contrary to expectations, the extent of viable but denervated myocardium seems to be associated with increased pain sensitivity in patients with recent myocardial infarction.