Mice infected intracerebrally (i.c.) with wild-type (wt) VSV or temperature-sensitive (ts) mutants, ts 11, ts 22, ts 31 and ts 41, were studied for the development of histopathological lesions in the central nervous system (CNS). Mice infected i.c. with wt VSV exhibited histopathological lesions consisting principally of occasional foci of perivascular mononuclear cell infiltration and rare foci of necrosis. All wt VSV infected mice died within 2 days of i.c. inoculation. In contrast, mice infected i.c. with ts 22 and ts 31 developed spongiform lesions limited to the grey matter of the spinal cord beginning 4 days after inoculation. The spongiform lesions rapidly spread to involve the entire grey matter of the spinal cord by 5-7 days after infection. Vacuolar changes were restricted principally to neuronal processes and astrocytes. Ts 22 and ts 31 infected mice developed neurological illness beginning 4 days after infection and the majority of mice died by 7 days after infection. Mice infected with ts 11 and ts 41, on the other hand, remained clinically well and were devoid of neuro-pathological lesions at 4 and 8 days after infection.