Lymphocytic interferon gamma (IFN-gamma) production and major histocompatibility complex (MHC) antigen induction were studied in experimental measles and vesicular stomatitis virus infections in the brain. Fifteen-day-old Sprague-Dawley rats injected intracerebrally with the HNT strain of measles virus showed already within 1 day after infection an increased number of cells producing IFN-gamma in the spleen, cervical lymph nodes and leptomeninges. These rats recovered after a transient neuronal infection in the brain. Rats infected intracerebrally with vesicular stomatitis virus, on the other hand, all succumbed after 2 days and showed no IFN-gamma production in lymphoid cells. Immunohistochemically MHC class I antigen appeared in infected and uninfected cells in the brain during replication of both viruses. A role for the recently discovered nerve fibres with IFN-gamma-like immunoreactivity, which are normally present in the brain, in the MHC antigen induction is discussed.