In a previous study of the brains of 15 adults with glioblastoma multiforme who received minimal or no radiotherapy we determined the topographic distribution of tumor cells. All 15 brains had been fixed and then cut in the coronal or horizontal plane. The distribution of neoplastic cells was determined and entered onto tracings of the whole mount histologic sections. The last CT scans obtained prior to death of 11 of the patients were reviewed independently by a neuroradiologist who traced, on the CT scans, the outer edge of both the contrast-enhancing area and the peritumoral low density "edema". Presented with the neuroradiologist's assessment of the contrast enhancing rim of tumor and of the "edema", a radiotherapist and a radiation dosimetrist, in the present study, prepared treatment plans for a 6 MeV linear accelerator. In 9 of the 11 cases in which immediately antemortum CT scans were available, radiation treatment of the contrast enhancing area alone with a 1 cm margin would have missed portions of the histologically identified tumor. Treatment of the contrast enhancing area along with the peritumoral "edema", with a 1 cm margin, would have covered histologically identified tumor in six of the 11 cases. Treatment of the contrast enhancing area, all "edema", and a 3 cm margin around the "edema" would have covered histologically identified tumor in all cases. Tumors tended to track along nerve pathways. In those lesions near the midline it was common for tumor to cross the corpus callosum. We conclude that radiotherapy with fields designed to treat the contrast enhancing region alone or this region plus "edema" with a tight margin will frequently miss tumor which can be histologically identified by our technique.