Interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. The present study is a report of a novel approach of targeting malignant glioma with IL-13R alpha 2-specific cytotoxic T lymphocyte (CTL) induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with human leukocyte antigen (HLA)-A2-restricted IL-13R alpha 2(345-353) peptide-pulsed T2 cells. The induced CTL showed specific lysis against T2 cells pulsed with the peptide and HLA-A2(+) glioma cells expressing IL-13R alpha 2(345-353), while HLA-A2 glioma cell lines that express IL-13R alpha 2(345-353) could not be recognized by CTL. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. These results suggest that the induced CTL specific for IL-13R alpha 2(345-353) peptide could be a potential target of specific immunotherapy for HLA-A2 patients with malignant glioma.