The intraocular injection of the Sindbis virus in adult BALB/c mice produces a uveoretinitis with little or no central nervous system involvement. Ocular disease starts on the third day after infection and presents as a mild to moderate iridocyclitis and retinitis, usually accompanied by typical severe dysplastic changes of the retina. The inflammatory infiltrate consists almost exclusively of lymphocytes and histiocytes. Immunosuppression of the mouse with cyclophosphamide on the day after infection markedly reduces or eliminates completely the inflammatory response, suggesting that the virus itself is not cytopathogenic. In the normal host, the virus replicates within the eye for several days but is then completely eliminated by day 8 after infection. In the immunosuppressed animal, virus titers reach greater levels than in the normal animal and then fall, in step with the developing inflammatory response. It would appear that the immunologic mechanisms responsible for clearance of the viral infection from the eye also mediate the ocular disease.