Denervation supersensitivity was demonstrated in anesthetized dogs 5 to 10 days after transmural myocardial infarction produced by latex embolization of a diagonal branch of the left anterior descending coronary artery. Sympathetic efferent denervation in noninfarcted myocardium apical to the infarction was demonstrated by a 90% depletion of myocardial norepinephrine content in the apical (45 ± 15 pg norepinephrine/g tissue) vs basal (437 ± 76 pg/g tissue) regions and by the lack of effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation in 34% of sites apical to the infarction. Supersensitivity in the area apical to the infarction was manifested by an exaggerated shortening of the ERP during both norepinephrine and isoproterenol infusions, with an upward and leftward shift in the dose-response curves in the apical vs basal regions (p < .001). The cellular mechanism for denervation supersensitivity did not involve detectable changes in the ,Badrenergic receptor adenylate cyclase system. There was no difference in the density of /3-adrenergic receptors ([1251]-cyanopindolol) in the apical (268.6 ± 22.7 fmol/mg protein) vs the basal (253.5 ± 24.8 fmol/mg protein) regions. Adenylate cyclase activity stimulated by guanosine triphosphate plus isoproterenol was slightly greater in the apical (58.7 ± 17.4%) than in the basal (49.6 ± 10.9%) region, but this difference did not reach statistical significance (p = .068). Muscarinic modulation of fl-receptor coupling (oxotremorine attenuation of guanosine triphosphate plus isoproterenol-stimulated adenylate cyclase activity) also was not significantly different at the apical (31.6 ± 17.5% inhibition) and basal (21.4 ± 20.9% inhibition) sites. These data show that a transmural myocardial infarction produces denervation supersensitivity in areas apical to the infarction, but in this preparation no differences in the total number or a redistribution of ,B-adrenergic receptors or adenylate cyclase activity were detected. Data from several studies indicate that efferent sympathetic nerves of the left ventricle course in the superficial subepicardium before diving transmurally, and travel in a basal-to-apical direction.0 15. 16 We have demonstrated that transmural myocardial infarction, presumably by affecting the postganglionic sympathetic nerves that traverse the area of infarction, produces sympathetic denervation in viable myocardium apical to the infarction. 7 We therefore reasoned that this area of myocardium might exhibit an exaggerated response to infused norepinephrine. We chose to investigate an electrophysiologic end point, shortening of effective refractory period (ERP), because it may be important in the development of arrhythmias.'`The purpose of this study was to test the hypothesis that transmural myocardial infarction produces sympathetic denervation supersensitivity in noninfarcted myocardium apical to the infarction.