Background and purpose In malignant glioma the presence of the IDH1 mutation (IDH1 R132H ) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy. Material and methods We determined the influence of IDH1 R132H mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity in vitro under normoxia (21% O 2 ) and hypoxia (<1% O 2 ) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1 wt ) and mutated IDH1 (IDH1 R132H ). Results Overexpression of IDH1 R132H in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1 R132H -positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF 10 : 1.52, p < 0.01 and 1.42, p < 0.01), U-343MG (DMF 10 : 1.78, p < 0.01 and 1.75, p < 0.01) and LN-229 (DMF 10 : 1.41, p < 0.05 and 1.68, p < 0.01) under normoxia and hypoxia, respectively. Conclusion Our data indicate that IDH1 R132H mutation causes both a less aggressive biological behavior and direct radiosensitization of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy. [ABSTRACT FROM AUTHOR]