Infections of the cornea with herpes simplex virus type 1 cause inflammatory lesions which frequently lead to blindness. The disease is suspected to be immunopathological in nature. To establish this point and to study possible mechanisms involved, corneal infections in C.B-17 scid/scid and cell-reconstituted scid mice were investigated. Whereas unreconstituted scid mice failed to develop herpetic stromal keratitis (HSK) and died of encephalitis, mice reconstituted with T lymphocytes generated severe lesions. T cells of the CD4+ subset were found to be essential mediators of the HSK lesion, while T cells of the CD8+ subset protected mice from lethality. The results confirm that HSK is an immunopathological disease and that scid mice provide a convenient model that should prove valuable in establishing the biochemical mechanisms by which HSK is mediated.