Herpetic stromal keratitis (HSK) is an immunopathological lesion involving herpes simplex virus (HSV) infection and CD4(+) T cells of the Th1 phenotype, but the nature of the target antigens which drive HSK remains uncertain. In the present report we show that ovalbumin TCR-transgenic mice backcrossed to SCID mice unable to recognize HSV show clinical signs of HSK but die of viral encephalitis before the lesions become severe. However, passive transfer of anti-HSV serum at 24 h clears virus and affords protection from both HSK lesions and death. Adoptive transfer of CD8(+) T cells at 72 h usually conferred protection but animals developed severe corneal pathology by 3 weeks post infection. At this time viral antigens were not demonstrable in the cornea and the T cells in the inflammatory lesions were CD4(+)KJ1-26.1 idiotype positive, i. e. OVA peptide specific. These results indicate bystander activation of CD4(+) T cells in a virus-induced inflammatory milieu. This mechanism of immunoinflammation may represent an important component of any lesion which involves CD4(+) T cells.