Immunologic differences exist between the peripheral and central cornea. The peripheral cornea is closer to the conjunctiva, which has all of the immunologic machinery necessary to generate an immune response. The peripheral cornea has more Langerhans' cells and IgM than the central cornea. The peripheral cornea also has more C1, the recognition unit of the classic pathway of complement, than the central cornea so that antigen-antibody complexes, whether formed in the cornea itself or whether derived from the tears, aqueous humor, or limbal vessels, may activate complement more effectively in the peripheral than central cornea. Autoimmune diseases that involve the peripheral cornea include Mooren's ulcer and collagen vascular diseases. The humoral- and cell-mediated autoimmune phenomena that are associated with Mooren's ulcer and its response to immunosuppressive therapy suggest that it is an autoimmune disease directed against the cornea itself. Collagen vascular diseases may be associated with peripheral corneal ulcers with or without scleritis. In these diseases, circulating immune complexes may lodge in the limbal vasculature causing an immune vasculitis or deposit in the peripheral cornea setting off the complement cascade. Peripheral corneal diseases that probably represent a hypersensitivity reaction to exogenous antigens include catarrhal infiltrates and ulcers and phlyctenules. In the United States today, these corneal lesions are generally associated with staphylococcal blepharitis. Experimental models suggest that hypersensitivity to Staphylococcus aureus cell wall antigens may be important to their immunopathogenesis.