Newborn NFS/N mice are susceptible to the neurological disease induced by infection with Cas-Br-M murine leukemia virus (Cas), and do not develop a protective cytotoxic T cell (CTL)-mediated response to Cas infection. Here we demonstrate that whole UV light-inactivated Cas (UV-Cas), inoculated in newborn NFS/N mice, induced a strong, Cas-specific CTL response detectable 2 weeks postinoculation and persisting in vivo for > or = 36 weeks. The magnitude of the UV-Cas-induced splenic CTL response, mediated by CD8+ T cells, inversely correlated with the level of proviral cas env sequences detectable in the spleen of the UV-Cas-inoculated mice, as revealed by PCR amplification of tissue DNA. The transfer of UV-Cas-primed splenocytes, with Cas-specific CTL activity, protected 100% of recipient newborn mice from the development of neurological disease induced by infection with live Cas, for more than 28 weeks, and reduced the level of viral replication in the recipients.