High grade malignant gliomas are among the most radioresistant human tumors and total doses up to 80 Gy are inadequate to achieve long-term local control in most of the patients. Hypoxia has been demonstrated in primary brain tumors and may be one of the reasons for their radioresistance. In experimental models carbogen breathing and nicotinamide have been shown to act against hypoxia by different mechanisms and both modalities were tested in 16 patients with supratentorial malignant gliomas in combination with a conventional radiotherapy scheme (50 Gy in 25 daily fractions). The present study was performed to determine the feasibility and toxicity of conventional radiotherapy combined with carbogen breathing and nicotinamide. The unexpectedly high incidence of acute liver toxicity, the possible increase of subacute and late CNS toxicity, and the absence of a higher effectivity led us to reconsider this new treatment modality for patients with malignant gliomas.