Background: According to one hypothesized mechanism of defibrillation, shocks directly excite the bulk of ventricular myocardium in the excitable state due to intramural virtual electrodes; however, this hypothesis has not been examined in intact myocardium. Objectives: The purpose of this study was examine the role of intramural virtual electrodes in shock-induced activation of intact left ventricular (LV) tissue. Methods: Twelve isolated porcine LV preparations were stained with a transmembrane potential (Vm)-sensitive dye by two methods: (1) surface staining and (2) global staining via coronary perfusion. Shocks (E ≈0.8-48 V/cm, duration = 10 ms) were applied across the wall from epicardium to endocardium during diastole via transparent electrodes. Shock-induced Vm responses were measured optically from the intact epicardial surface after surface staining and global staining. Results: Surface-staining recordings demonstrated different Vm responses to cathodal and anodal shocks. Whereas cathodal shocks caused depolarization and rapid activation of the epicardial surface, anodal shocks induced hyperpolarization and delayed surface activation. In contrast, global-staining Vm responses to cathodal and anodal shocks were qualitatively similar. Both responses were characterized by activation with small latency and rapid propagation. Weak shocks of both polarities induced monotonic action potential upstrokes; stronger shocks induced nonmonotonic upstrokes with two rising phases at shock onset and end. Such features of global-staining Vm responses as make activation of the epicardium by anodal shocks and the nonmonotonic action potential upstrokes can be explained by the presence of subepicardial intramural virtual electrodes. Conclusion: These data suggest that shocks induce intramural virtual electrodes that directly excite LV tissue and account for the shape of optical Vm responses recorded from the epicardial surface. © 2006 Heart Rhythm Society.