Cancer vaccines are one approach for the treatment of brain tumors. Most experimental studies are performed on so-called "immunogenic" brain tumor models such as the rat 9L glioma which does not reflect characteristics of human glioblastoma. In the present study, we tested syngeneic cellular vaccinations alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) on the weakly immunogenic F98 glioma model. Previous studies have shown the efficacy of this treatment on the 9L glioma model. Fisher rats received an intracerebral implantation of F98 cells. Three days later, two subcutaneous vaccinations with irradiated F98 cells were realized in presence or absence of GM-CSF. This scheme of vaccination induced a systemic cellular and humoral immune response capable of in vitro cytolytic activity against F98 cells. However, no significant differences in survival times were noted between vaccinated and untreated animals. Animals vaccinated with GM-CSF or without GM-CSF had respectively a survival time of 26 +/- 2.1 and 25 +/- 4.4 days following tumor challenge versus 26.5 +/- 2.4 days for untreated rats. Fourteen days after the intracerebral tumor implantation, the tumors of vaccinated animals showed a robust infiltration by T lymphocytes, NK cells, dendritic cells, granulocytes and CD11b/c+ myeloid cells. This infiltration was nearly absent in untreated animals except for CD11b/c+ myeloid cells. This study shows that, contrary to the 9L glioma model, the F98 glioma model is resistant to syngeneic cellular vaccinations although a strong peripheral and intratumoral immune response can be induced. These results suggest that the F98 glioma is an attractive model to understand the mechanisms of glioma immunotherapy resistance.