AbstractThe effect of virus dose and animal age on the appearance of acute and latent neurologic infection by HSV1and HSV2was studied in Balb/c and ICR mice inoculated in the footpad. At low viral doses HSV2was found to be 1,500 times more neurovirulent than HSV1. At high doses there was no difference in neurovirulence. Age‐acquired resistance to disease was shown to be less complete with HSV2than with HSV1. Neurovirulence was shown to be associated with spread of infection to the spinal ganglia. The data indicate that the factor(s) responsible for the differential neurovirulence of these two viruses is related to events at the level of the footpad and/or sciatic nerv