Systemic immunization of rabbits with herpes simplex virus (HSV) had two opposite effects on the outcome of subsequent efforts to produce primary HSV uveitis, the difference depending on whether or not the rabbits had had nonherpetic uveitis before the HSV challenge. In normal eyes, systemic immunization with HSV provided complete protection against the production of primary uveitis by an intraocular injection of HSV; but in eyes that had had a bout of experimentally induced nonherpetic uveitis before the challenge, the same systemic immunization was not protective. In these eyes, an immune-mediated uveal inflammation developed. Nonherpetic uveitis had apparently "primed" the eyes of the HSV-immune rabbits for subsequent immune-mediated HSV uveitis.