Between 1983 and 1987 the Radiation Therapy Oncology Group conducted a prospective phase II study to evaluate survival in primary non-Hodgkin's lymphoma of the brain treated with whole brain irradiation to 40 Gy and a 20 Gy boost to tumor plus a 2 cm margin. Forty-one patients are reported. Full follow-up is available on 35/41 who have died. Six are alive at 8.8-67.2 months from start of radiation therapy with a median followup of 53.9 months. Overall median survival was 11.6 months from start of radiation therapy and 12.2 months from diagnosis, with 48% surviving 1 year and 28% surviving 2 years. Karnofsky Performance Status and age were significant prognostic factors. Patients with a Karnofsky Performance Status of 70-100 had a median survival of 21.1 months compared to 5.6 months for patients with a status of 40-60 (p less than .001). Fourteen patients less than 60 years of age had a median survival of 23.1 months, while 27 patients greater than or equal to 60 years of age had a median survival of 7.6 months (log-rank p = .001). Disease recurred in the brain in 25/41 (61%) of the patients, (21/41 in the brain only and 4/41 in the brain plus distant metastases). Despite high dose and large volume irradiation, primary Central Nervous System lymphoma still exhibits excessive mortality, especially in older patients. This paradox of the relative radioresistance of primary Central Nervous System lymphoma remains unresolved.