We tested adjuvant chemotherapy combining dibromodulcitol (DBD) and bischloroethylnitrosourea (BCNU) given postoperatively to adults with newly diagnosed supratentorial malignant gliomas. We enrolled 269 patients, 255 of whom were eligible. After surgery, we treated all patients with radiation therapy, using a median dose of 60 Gy given in 30 fractions. After randomization, patients in the chemotherapy group also received (1) six weekly courses, administered during irradiation, of DBD 700 mg/m2 and (2) one to nine (median, four) courses, administered during the first year following radiation therapy, of DBD 1,000 mg/m2 on day 1 and BCNU 150 mg/m2 on day 2, with the course being repeated every 6 weeks. Patients treated with radiation therapy along with DBD plus BCNU (group 2) had significantly longer survival time (p = 0.044) and time to progression (p = 0.003) than did those treated with radiation therapy alone (group 1). The median survival time was 13.0 months for group 2 and 10.4 months for group 1; the median time to progression was 8.1 months for group 2 and 6.7 months for group 1. The percentage of patients alive at 18 and 24 months was 34% and 21% in group 2 compared with 21% and 12% in group 1. DBD plus BCNU is an effective adjuvant therapy for malignant glioma.