Experimental autoimmune uveoretinitis (EAU) induced by retinal antigens is a CD4+ (Th) lymphocyte mediated disease. Generation of autoreactive CD4+ cells requires the processing and presentation of autoantigen by antigen presenting cells (APC) in combination with MHC Class II antigen. Efficient presentation of antigen to T cells has also been shown to depend on accessory molecules of adhesion such as intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1). Aberrant expression of Class II antigens by local tissue cells has been suggested as a possible mechanism in autoimmune processes. Several ocular cells express Class II antigens during inflammation, while other cells such as Muller cells inhibit antigen presentation in vitro. We have also shown that retinal pigment epithelial cells (constitutively) and endothelial cells (after induction) express ICAM-1 and that CD4+ lymphocyte adhesion to these cells is inhibited by antibodies to ICAM-1. Accessory molecules may therefore be important, not only in local presentation of antigen but in recruitment of circulating autoreactive cells to the eye since these cells represent the site of the blood-retinal barrier. Regulation of the local immune response in the eye therefore, may occur at several levels.