Wallerian degeneration, the disintegration of the distal part of an injured axon, is an important event in many neurodegenerative diseases. We studied Wallerian degeneration in dorsal root ganglion (DRG) explants in culture by separating neurites from their cell bodies with a scalpel. The severed neurites showed Annexin V positive staining, that spreads distally with a rate comparable to that of slow axonal transport in intact neurons in vivo. Moreover, the injured neurites showed loss of mitochondrial membrane potential. These features resemble those seen when cells undergo apoptosis. These data contribute to a new understanding of the mechanism of axonal degeneration, have implications for the response of stromal cells in central nervous system (CNS) and raise the prospect of new pharmacological treatments for those neurodegenerative pathologies where the protection of the cell body alone does not alleviate the disease.