Corneal infection with herpes simplex virus in mice induces an inflammatory response in the stroma (herpetic stromal keratitis (HSK)) that appears to represent an immunopathologic reaction in which T cells of the CD4+ subset act as the essential participants. To assess the role of T cell cytokines at different clinical phases of HSK, corneas and draining lymph node (DLN) cells were collected and the levels of mRNA thought to be representative of type 1 and type 2 T cells were quantitated by reverse transcription-PCR. In the corneas collected before the onset of clinical disease, IFN-gamma and IL-4 mRNA were detectable, with levels of IFN-gamma 5- to 15-fold higher than IL-4. During the onset and peak expression of clinical disease, type 1 cytokines IFN-gamma and IL-2 were predominant in the corneas, and IL-4 levels were either very low or undetectable. Neither IL-10 nor IL-5 mRNA was present. After 3 wk postinfection, when some animals with mild disease began to recover, high levels of type 2 cytokine mRNA, particularly IL-10, were present. In addition, only during the recovery phase was IL-10 mRNA present in DLN samples. Levels of transcriptional activity for cytokine mRNA during clinical HSK were higher in corneas than in the corresponding DLN samples. The results indicate that IL-10 may be involved in HSK resolution and that the stimuli for cytokine induction in the cornea may differ from those in the DLN.