Müller cells have been shown to have a dual effect in vitro on autoimmune T helper lymphocytes. In a coculture system, Müller cells have a primary inhibitory effect on the proliferation of T lymphocytes. In conditions where their inhibitory action is suppressed, Müller cells can, however, stimulate T cells. In the present study we evaluated the in vivo effect of Müller cells on actively induced experimental autoimmune uveoretinitis (EAU). Ten millimoles of L-alpha-aminoadipic acid (L-AAA), a specific gliotoxic agent, was injected into the vitreous of one eye of Wistar-Furth (WF) rats (a low EAU responder) on the day of immunization. Control rats were injected similarly with phosphate-buffered saline alone. The rats were immunized with S-antigen in CFA or in CFA alone. The results demonstrate that the incidence of EAU increases twofold in the eyes receiving an intravitreal injection of L-AAA in comparison to the contralateral eyes not receiving an injection. No such difference in EAU incidence was observed in control animals. Some rats that had been immunized with CFA alone after an intravitreal injection of L-AAA demonstrated a small amount of retinal perivascular inflammatory cell infiltrate but did not develop typical EAU lesions. The retinal vasculature was normal on examination by fluorescein angiography after injection of L-AAA. These data suggest that Müller cells can influence the course of uveoretinitis through their interaction with T cells.