The expression, and cytokine modulation, of major histocompatibility complex (MHC) class I and class II molecules on oral and skin keratinocytes were compared in cell culture. Both cell types expressed class I, but not class II, constitutively. However, stimulation with interferon-gamma, but not interleukin-1 alpha, and -1 beta, tumour necrosis factor-alpha or lymphotoxin, induced increased expression of class I and de-novo expression of HLA-DR on both cell types. Oral keratinocytes differed from skin keratinocytes in that they exhibited greater sensitivity to interferon-gamma stimulation and higher stimulated expression of both class I and HLA-DR. In addition, interferon-gamma stimulated oral, but not skin, keratinocytes to express HLA-DP and -DQ. These observations suggest that, like skin keratinocytes, under certain conditions, dial keratinocytes may be able to act as antigen-presenting cells. This may be important in the initiation and progression of some immune-mediated mucocutaneous diseases. Moreover, differences in MHC expression may help to explain differences in the presentation of these diseases on the skin and oral mucosa. Copyright (C) 1996 Elsevier Science Ltd.