Corneal inoculation of Nude (athymic) mice and Balb/c mice with herpes simplex virus Type I produces a brainstem encephalitis with demyelination of the trigeminal root entry zone. The extent of CNS demyelination is less in the immune-deficient athymic mice 7 days after infection compared to the immune-competent Balb/c mice. Both groups demonstrate a macrophage response and beginning myelin disruption approximately 3 days after corneal infection when herpes viral particles are first observed within central nervous system cells. Five to seven days after infection when differences in the extent of demyelination between the immune-competent and immune-deficient animals become evident, the Balb/c mice demonstrate T cells and increasing numbers of macrophages at the trigeminal root entry zones. These findings suggest an interaction between macrophages and T cells which leads to an extension of the demyelination in the immune competent Balb/c mice and that lack of T cells is important in limiting demyelination in Nude (athymic) mice.