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, oral 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.