Radiation therapy is routinely used in the management of primary central nervous system malignancies. However, the efficacy of this therapeutic modality is limited by the occurrence of resistance. In the present study, we investigated whether modulation of oxidative stress might underlie glioma cell radioresistance. Superoxide dismutase activity in irradiated M059J cells was two-fold higher than that in untreated controls, but did not significantly change in U-87 and U-138 cells. This is accompanied by an increase in reactive oxygen species content and decreases in cells viability. Pharmacological or genetic modulation of oxidative stress could be associated with an enhancement in the susceptibility of tumor cells to radiation therapy.