Experimental autoimmune anterior uveitis (EAAU), a model of uveitis induced by sensitization to melanin associated antigen (MAA) derived from the iris and ciliary body, closely resembles human acute anterior uveitis. The immunopathogenesis of EAAU was studied by immunohistochemical detection of immune cells and the expression of Ia, ICAM-1 and LFA-1 antigens. Male Lewis rats were immunized with bovine MAA, mixed with CFA and pertussis toxin in the hind foot pad. Animals were examined daily by slit-lamp biomicroscopy and serially sacrificed up to 30 days. Immunohistology of the enucleated eyes was performed with monoclonal antibodies W3/25 (CD4), OX-8 (CD8), ED2 (macrophage), OX-33 (B cell), OX-6 (Ia), IA29 (ICAM-1) and WT.1 (LFA-1). During each stage of EAAU, CD4+ T cells predominated over both CD8+ T cells and macrophages in the uvea. Very few B cells were detected during each stage of EAAU. EAAU could not be induced by the adoptive transfer of sera obtained from immunized animals. Low levels of constitutive ICAM-1 and Ia were observed. An increase in ICAM-1 expression was first noted on the epithelial cells of the uveal tract and RPE on day 9 post immunization and preceded LFA-1 and Ia upregulation by approximately 2 days. The immunopathogenesis of EAAU appears to be linked to the presence of the CD4+ T cells.