Several T lymphocyte clones (TLC), specific for a p21-Ras-derived peptide expressing a Gly13-->Asp mutation and of the CD8+ subtype, were generated from peripheral blood of a colon carcinoma patient. The TLC exerted cytotoxicity against an interferon-gamma (IFN gamma)-pretreated colon carcinoma cell line, HCT116, which harbours the Gly13-->Asp mutation and shares both HLA-A2 and HLA-B12(44) with the patient. This cytotoxic effect could be blocked by a monoclonal antibody (mAb) against CD8 molecules, as well as with a mAb against HLA class I molecules and a polyclonal antiserum against HLA-B12, identifying B12(44) as the antigen-presenting molecule. In growth-inhibition experiments, the growth of both IFN gamma-pretreated and untreated target cells were strongly inhibited by the presence of the CD8+ TLC. Together these data indicate that human cancer cells harbouring a spontaneous ras mutation can process aberrant p21 Ras and express peptide/HLA-class-I complexes on their surface in sufficient density to be recognized by Ras-specific cytotoxic T lymphocytes.