Fas antigen, which belongs to a nerve growth factor/ tumor necrosis factor receptor superfamily, is a membrane protein that induces apoptosis. In humans, distribution of Fas antigen has been reported on cell lines and lymphocytes. Immunohistochemical studies revealed Fas antigen on the keratinocytes of lesional epidermis in lichenoid drug eruption, erythema multiforme, contact dermatitis, bullous pemphigoid, pemphigus vulgaris, and herpes zoster; it is co-expressed with intercellular adhesion molecule-1. Cultured keratinocytes expressing Fas antigen increased from 8.4% to 34.6% after stimulation with interferon gamma for 24 h. Treatment of interferon-gamma – stimulated keratinocytes with anti-Fas for 48 h resulted in DNA fragmentation and death of 32% of cells, suggesting that Fas antigen may mediate apoptosis. The expression of Fas antigen on keratinocytes in lesional skin suggests that death via Fas antigen may play an important role in the pathogenesis of keratinocyte cytotoxicity.