Background: Recent studies suggest that during ventricular fibrillation (VF) epicardial vessels may be a site of conduction block and the posterior papillary muscle (PPM) in the left ventricle (LV) may be the location of a "mother rotor." The goal of this study was to obtain evidence to support or refute these possibilities. Methods: Epicardial activation over the posterior LV and right ventricle (RV) was mapped during the first 20 s of electrically induced VF in six open-chest pigs with a 504 electrode plaque covering a 20 cm2 area centered over the posterior descending artery (PDA). Results: The locations of epicardial breakthrough as well as reentry clustered in time and space during VF. Spatially, reentry occurred significantly more frequently over the LV than the RV in all 48 episodes, and breakthrough clustered near the PPM (p∈<∈0.001). Significant temporal clustering occurred in 79% of breakthrough episodes and 100% of reentry episodes. These temporal clusters occurred at different times so that there was significantly less breakthrough when reentry was present (p∈<∈0.0001). Conduction block occurred significantly more frequently near the PDA than elsewhere. Conclusions: The PDA is a site of epicardial block which may contribute to VF maintenance. Epicardial breakthrough clusters near the PPM. Reentry also clusters in space but at a separate site. The fact that breakthrough and reentry cluster at different locations and at different times supports the possibility of a drifting filament at the PPM so that at times reentry is present on the surface but at other times the reentrant wavefront breaks through to the epicardium. © Springer Science+Business Media, LLC 2008.