In this study, we describe the ultrastructural and immunocytochemical changes that occur in the iris of rats with experimental autoimmune uveoretinitis (EAU). General changes include perivascular infiltration of inflammatory cells, followed by hemorrhage and extensive tissue destruction. Alterations in the iris epithelium were also noted. A breakdown in the blood-iris barrier was demonstrated in some vessels at the peak of inflammation; peroxidase reaction product was seen in the basement membrane and perivascular spaces. We found that, in inflamed iris vessels, endothelial cells and smooth muscle cells become hypertrophic and show increased amounts of synthetic organelles. This finding is similar to our previous observations on endothelial cells and smooth muscle cells in retinal vessels in EAU. In addition, as was reported in the retinal vascular basement membrane in EAU, there is an increase in immunoreactivity of several extracellular matrix molecules in the iris vascular basement membrane; during inflammation, there is a significant increase in immunoreactivity of collagen types I and III, entactin, fibronectin, and laminin. Activated endothelial cells and smooth muscle cells are likely to be involved in the synthesis of certain of these matrix molecules.