The gene for the human poliovirus receptor (hPVR/CD155) is the founding member of a new family of genes encoding proteins belonging to the immunoglobulin superfamily. To determine whether CD155 is expressed during mammalian development, we have made use of the previously characterized promoter of the CD155 gene and generated mice transgenic for a CD155 promoter-driven beta-galactosidase reporter gene. Expression of the reporter gene in transgenic embryos was observed during midgestation in anterior midline structures of the developing central nervous system and in the neuroretina. During that period, reporter gene expression appeared within the notochord and floor plate along the entire spinal cord reaching into the caudal diencephalon. In addition, transgene expression was observed in axonal projections emanating from retinal ganglion cells forming the optic nerve to reach the future region of the optic chiasm. Analysis of expression of CD155 during human embryonic development confirmed the distribution of reporter gene expression specified by CD155 promoter activity. The anatomical distribution of CD155 promoter activity during embryogenesis matches that of transacting factors previously identified to regulate transcription of the CD155 gene. Expression of CD155 within embryonic structures giving rise to spinal cord anterior horn motor neurons may explain the restrictive host cell tropism of poliovirus for this cellular compartment of the CNS.