The paucity of mammalian adult cardiac myocytes (CM) proliferation following myocardial infarction (MI) and the remodeling of the necrotic tissue that ensues, result in non-regenerative repair. In contrast, zebrafish (ZF) can regenerate after an apical resection or cryoinjury of the heart. There is considerable interest in models where regeneration proceeds in the presence of necrotic tissue. We have developed and characterized a cautery injury model in the giant danio (GD), a species closely related to ZF, where necrotic tissue remains part of the ventricle, yet regeneration occurs. By light and transmission electron microscopy (TEM), we have documented four temporally overlapping processes: (1) a robust inflammatory response analogous to that observed in MI, (2) concomitant proliferation of epicardial cells leading to wound closure, (3) resorption of necrotic tissue and its replacement by granulation tissue, and (4) regeneration of the myocardial tissue driven by 5-EDU and [3H]thymidine incorporating CMs. In conclusion, our data suggest that the GD possesses robust repair mechanisms in the ventricle and can serve as an important model of cardiac inflammation, remodeling and regeneration. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.