The spatial and temporal patterns of apoptosis and proliferation in timed fetal, neonatal, and adult murine hearts have been determined using an in situ end-labeling technique for detecting fragmented DNA, and bromodeoxyuridine immunofluorescence as a marker for DNA synthesis. Also, cardiac expression of apoptosis-related proteins was assessed by immunofluorescence. Prominent apoptotic labeling was found in the right ventricular subendocardium and the basal septum in the area of the developing conduction system. In the right ventricle, apoptotic labeling surged late in the first day postpartum, then declined to levels similar to the left ventricle by postpartum day 8.5. Apoptotic labeling at the basal septum was greatest peripartum and gradually declined to levels seen in the rest of the heart by postpartum day 8.5. Cessation of proliferation did not occur simultaneously throughout the neonatal heart. Through postpartum day 4.5, incorporation of BrdU was greater in the left ventricle than in the right ventricle, particularly in the subendocardium. Bax and Fas, proapoptotic proteins, were detected homogeneously throughout both ventricles in the neonate, while Bcl-2, an antiapoptotic protein, was not detectable. These data suggest that postnatal cardiac remodeling results from changes in both apoptosis and proliferation. Furthermore, the temporal and spatial pattern of these processes, coincident with the hemodynamic changes associated with parturition, suggests that both processes may be regulated by mechanical factors. © 2001 Wiley-Liss, Inc.