We treated 23 patients with primary central nervous system lymphoma with a protocol of conventional radiation up to 55 +/- 5 Gy followed by 4 to 6 cycles of intravenous doxorubicin (30 mg/m2), vincristine (1 mg/m2) and cyclophosphamide (350 mg/m2), and oral prednisolone (8-30 mg/m2) (VEPA chemotherapy) repeated at 2-week intervals. The median age of the 23 patients was 59 years, and the median World Health Organization performance status score was 2. Seventeen patients received 4 or more courses of the chemotherapy, but 6 received only 1 or 2 courses for various reasons. The median survival time for all 23 patients was 25.5 months and their 5-year survival rate was 23%. These values were 34 months and 32%, respectively, for the 17 patients who received 4-6 courses of chemotherapy. After treatment, decline in performance status unaccompanied with tumor recurrence was observed in 44% of the patients; the incidence was apparently higher in older than in younger patients. The survival results obtained with this combined radiochemotherapy regimen appear to be better than those reported in most previous studies of patients treated with radiation alone. Post-irradiation VEPA chemotherapy appears to be worthy of further evaluation.