The septohippocampal projection was used to study the survival following axotomy, axonal regeneration, and sprouting of a defined group of central neurons. Septohippocampal projection neurons in adult rats were axotomized by bilateral lesions of the fimbria-fornix. Using prelabeling prior to axotomy, intracellular staining, electron microscopy, and immunocytochemical and in situ hybridization techniques, we were able to demonstrate that the majority of septohippocampal neurons survived after axotomy. At least in young postnatal rats, these axotomized neurons have the capacity to regenerate an axonal process that reinnervates its appropriate target tissue, the hippocampus. We demonstrated this by axotomizing young septohippocampal neurons and co-culturing them with sections of hippocampus. Septohippocampal neurons appear to retain their capacity for axonal growth in adulthood, since they are able to sprout within hippocampal layers partially denervated by removing entorhinal afferents. In this paradigm the terminals of septohippocampal neurons themselves were not lesioned. Our results point to a previously underestimated capacity of septohippocampal neurons for survival following axotomy, regeneration, and sprouting.