Immunization and immunosuppression were evaluated during latent ocular herpes simplex virus, type 1 (HSV-1) infection in the rabbit, using the following parameters: (1) ability to recover virus from preocular tearfilm cultures; (2) reactivation of latent infection by direct electrical stimulation; and (3) recovery of virus from latently infected ganglia by whole-cell co-cultivation. Immunization prior to ocular inoculation of virus significantly reduced both the titer of virus shed into the tearfilm and the duration of virus shedding during primary ocular infection. Half of the non-immunized control rabbits died secondary to virus encephalitis, whereas none of the immunized rabbits died. The immunized rabbits could not be induced to shed virus by electrically stimulating the trigeminal ganglion directly. Immunosuppression of latently infected rabbits with high-dose cyclophosphamide (300 mg kg-1) enhanced virus shedding in the tearfilm and increased mortality due to viral encephalitis. Low-dose cyclophosphamide immunosuppression (40 mg kg-1) did not increase mortality because of viral encephalitis. Tearfilm virus shedding secondary to electrical induction in high-dose and low-dose cyclophosphamide animals was higher than that of control, non-immunosuppressed animals.