Intracranial inoculation of neonatal mice of certain inbred strains with Pichinde virus has been found to be fatal, but Balb/c neonates survive such infection. Survival of Balb/c mice after neonatal inoculation was not linked to the major histocompatability complex. Virus was gradually cleared in surviving Balb/c mice but could be detected in the brain and kidneys for up to 9 months after infection. These animals were not immunologically tolerant but exhibited high antibody titers to viral antigens. MHC restricted cytotoxic T cell activity was also demonstrable in persistently infected mice following challenge with high titered virus. Pathological changes consistent with glomerulonephritis were observed in the kidneys and surviving mice were runted compared to normals. This model differs from the widely studied persistent infection of mice with lymphocytic choriomeningitis virus (LCMV) and provides a unique model for the study of the genetics of resistance to viral infection, mechanisms of persistence and pathological processes in chronic viral infections.