We examined the in vitro cytotoxic activity of cutaneous T‐cell lines and clones from lichen planus (LP) patients against autologous epidermal keratinocytes. T cells were cultured from LP lesions and adjacent clinically normal skin and cloned by limiting dilution. Keratinocytes were cultured from LP lesions and adjacent clinically normal skin and immortalized by transfection with the E6 and E7 genes from human papillomavirus 16 (HPV16). The lesional T‐cell line from one LP patient contained 27% γδ+ T cells and was significantly more cytotoxic against autologous lesional keratinocytes than the T‐cell line from clinically normal skin. Clones isolated from the lesional T‐cell line were significantly more cytotoxic against autologous lesional keratinocytes than clones isolated from the non‐lesional T‐cell line. Most cytotoxic clones from LP lesions were CD8+ and most non‐cytotoxic clones from LP lesions were CD4+. One cytotoxic clone was CD4– and CD8– and expressed the γδ T‐cell receptor. Two CD8+ LP lesional T‐cell clones showed dose‐dependent killing of HPV16 E6/E7‐immortalized autologous lesional and normal keratinocytes, but no cytotoxic activity against Epstein–Barr virus‐transformed autologous B‐cell blasts. The cytotoxic activity of CD8+ lesional T‐cell clones against autologous lesional keratinocytes was partially blocked with anti‐major histocompatibility complex (MHC) class I monoclonal antibodies. These data support the hypothesis that CD8+ lesional T cells recognize an antigen associated with MHC class I on lesional keratinocytes and that CD8+ cytotoxic T cells lyse keratinocytes in LP lesions.