Purpose: To review our experience with pre-radiation chemotherapy for malignant glioma. Methods: Consecutive adults with newly diagnosed glioblastoma, anaplastic astrocytoma, anaplastic oligodendroglioma and anaplastic mixed glioma with a Karnofsky Performance Score of 60 or greater were treated with one cycle of procarbazine, lomustine and vincristine or lomustine alone, prior to radiation. Computed tomographic scans were obtained soon after surgery, eight weeks later, after radiation, and at regular intervals thereafter. The effects of chemotherapy and subsequent radiation and durations of tumor control and survival were assessed in this single arm, single center, prospective trial. Results: Thirty-seven patients started chemotherapy, 36 were rescanned eight weeks after diagnosis. Five patients (16%) responded to the first cycle of chemotherapy, three had glioblastoma and two anaplastic oligodendroglioma. Seven (19%) progressed during the first cycle, 6 had glioblastoma; with the addition of radiation one progressive case responded, three stabilized, and three continued to progress. Median times to progression and median durations of survival were 26 weeks and 60 weeks for the entire group, 24 weeks and 44 weeks for glioblastoma, and greater than 104 weeks for anaplastic astrocytoma. Conclusions: Most patients with glioblastoma do not respond to one cycle of nitrosourea-based chemotherapy given prior to radiation, but patients with anaplastic oligodendroglioma sometimes do. Patients with anaplastic astrocytoma may not respond to one cycle of chemotherapy, but often respond to subsequent radiation. Judging by survival results, radiation can be delayed eight weeks without appearing to compromise patient outcome. Implications: Pre-radiation chemotherapy with newer agents can be evaluated more fully in the future knowing that brief delays in radiation are unlikely to yield substantially inferior results.