Four glioma cell lines not expressing human leukocyte antigen (HLA)-DR or DQ did so after transfection with genes encoding HLA-DR and DQ. The glioma cells had enhanced ability to stimulate allogeneic and autologous responding lymphocytes in the mixed lymphocyte response (MLR). Glioma cells expressing only HLA-DR had weaker MLR enhancement than those expressing both HLA-DR and DQ or only HLA-DQ. Stimulation by transformed glioma cells increased the killing activity of responding lymphocytes against autologous glioma cells 2.0 times. Both HLA-DR and DQ are important in MLR, and the immunogenicity of glioma cells might be increased by transfection with genes encoding these antigens.