To analyze the role of the retinal vascular endothelial cells in the development of experimental autoimmune uveitis (EAU), we studied the presence of Ia antigen and FN in retinal vessels of Lewis rats immunized with retinal S antigen. Immunopathologic studies were performed on frozen tissues obtained during various stages of the disease. Our results show that Ia antigen was not present in the normal rat retina, and there was very little FN present in a few retinal vessels. One to two days prior to the histologic and clinical onset of EAU, FN was found to be increased in the retinal vessels. Ia antigen was found to be present in the retinal vessels coincident with the first signs of cellular infiltration. During the stage of maximal cellular infiltration, FN was present diffusely throughout the retina, as well as in the subretinal space, and Ia antigen was found diffusely in the cellular infiltrate. Therefore, FN and Ia antigen reflect the immunomodulation of vascular endothelial cells in EAU, which may be very important in the pathogenesis of retinal S antigen-induced uveitis. Two possible mechanisms for the role of the activation of the retinal vascular endothelium in the development of retinal inflammation in uveitis are discussed.