The concept of an immunopathogenesis in the establishment and progression of the recurrent aphthous stomatitis (RAS) lesion is well accepted. In this study the expression of Class I and Class II major histocompatibility complex (MHC) antigens on the epithelial cells in the preulcerative, ulcerative and healing phases of RAS lesions was investigated using monoclonal antibodies in an immunohistological technique. Both Class I and Class II MHC antigens were found on the basal cells in preulcerative lesions. As the lesions progressed to the ulcerative phase, antigen expression occurred on the cell membranes throughout the entire thickness of the epithelium. With healing, the expression of both Class I and Class II MHC antigens on epithelial cells declined to a stage where there was little or no detectable antigen on the cell membranes. Although cytotoxicity of epithelial cells in RAS lesions is accepted, the role of MHC antigen expression on these cells is uncertain and remains to be ascertained. Nevertheless, the results of the present study indicate that MHC antigens are expressed by epithelial cells in RAS and their expression follows a defined sequence.