Herpes simplex viruses (HSV) produce age-dependent encephalitis characterized by more severe involvement of the cerebral cortex in younger hosts. To elucidate the potential role of the major neural entry receptor of HSV, nectin-1, in age-dependent susceptibility of cortical neurons to viral encephalitis, the authors examined the anatomical distribution of the receptor protein in the developing human and mouse cerebral cortex, hippocampus, and cerebellum by immunohistochemistry. Nectin-1 is expressed at high levels in guiding cells (radial glial cells and Cajal-Retzius cells) that regulate radial migration of neurons in cortical lamination, at lower levels in migrating neurons, and at variable levels in the transient ventricular and marginal zones of the cerebral cortical wall. These results may have implications regarding the selective spatiotemporal tropism of HSV to specific neuronal populations, and for the better understanding of neurodevelopmental defects caused by fetal HSV infections.