Mice homozygous for the grey tremor (gt) mutation develop an accrelated spongiform encephalopathy similar to that exhibited by NFS/N mice infected with the wild mouse ecotropic virus, Cas- Br-M. Newborn NFS/N mice inoculated with cell-free extracts of gt brains developed tremor and paralysis associated with spongiform changes in brain indicating that the disease was transmissable. Murine retroviruses and scrapie-associated fibrils (SAF) were not detected in gt or recipient brains suggesting that the disease is caused by an unconventional agent different from scrapie-like agents. Resistance to ectromelia virus infection in vivo was shown to develop normally in mice depleted of L3T4+ cells. Depleted mice had virus-specific cytotoxic T lymphocyte (CTL) responses equal to those of normal mice indicating that help provided by L3T4+ T cells is not required for induction of CTL responses to modified self determinants in vivo.