The role of nerve growth factor (NGF) and of the neurotrophin receptor p75 (p75(NTR)) in programmed cell death was investigated in the retina and the spinal cord of mouse embryos. Large numbers of cells express p75(NTR) in and along the developing optic nerve and in the mantle zone of the spinal cord. In embryos carrying deletions in the ngf or the p75(NTR) gene, cell death was reduced in the retina and in the spinal cord. Increased numbers of Islet-1-immunoreactive cells were detected in the dorsal spinal cord, and the mantle zone was enlarged in both mutants. These results indicate that NGF/p75(NTR)-dependent mechanisms are used to remove cells when axonal tracts elongate in developing neuroepithelia.