Five immunosuppressive and anti-inflammatory agents were tested for their effects on development of experimental autoimmune uveoretinitis (EAU) and immune responses to S-antigen in rats immunized with this retinal antigen. When administered daily from day 0-14 after immunization, cyclosporine at 5-20 mg/kg was nontoxic and yet effective in inhibiting the development of EAU for at least 30 days. Allother tested drugs were found toxic at their immunosuppressive doses. Of these drugs, only cyclophosphamide (at 5-20 mg/kg) was capable of inhibiting EAU in some of the treated rats for up to 30 days. Bredinin (40-100 mg/kg), dexamethasone (0.2-0.4 mg/kg) or colchicine (0.5 mg/kg) produced only a delay in the disease onset. Cyclosporine was also unique in its effect on the immune responses of the rats by selectively inhibiting only the specific T-cell-mediated responses to S-antigen (delayed skin response and lymphocyte response in culture), while having no negative effect on antibody production or the lymphocyte response to the polyclonal mitogen, concanavalan A. Other drugs, when effective, inhibited all types of immune response. Cyclosporine was capable of preventing EAU even when given to rats as late as from day 7 after immunization. Only cyclophosphamide (at 20 mg/kg per day) had a similar effect on 1/3 of the rats, while other drugs only delayed or had no effect on the disease onset when given by this late schedule.