OBJECTIVE We report the results of a pilot study of the use of accelerated radiation therapy for 10 patients with primary lymphoma of the brain. METHODS There were five females and five males with a median age of 60 years (range 31-77 years) and a median Karnofsky performance status of 60 (range 30-90). Nine patients underwent biopsies only and one patient underwent a partial resection. The radiation therapy consisted of 50 Gy in 25 fractions over 13 consecutive days to the whole brain including all meningeal surfaces. Two fractions were delivered daily with a minimum interval of 6 h between fractions. Treatment was delivered daily right through the weekend with no treatment interruptions. RESULTS To date nine patients have died. The median survival was 17 months. Seven patients have demonstrated definite evidence of recurrence (six in the brain and one with positive CSF cytology only). There have been two autopsies, one of which demonstrated diffusely recurrent tumor and the other showing residual disease and radiation demyelination and small areas of necrosis in the pons which undoubtedly was the cause of death at 5 months. One patient alive and free of recurrence at 69 months has bilateral radiation retinopathy and an undiagnosed degenerative neurologic condition. CONCLUSIONS We conclude that this accelerated schedule of radiation therapy is ineffective in improving survival in primary lymphoma of the brain and is associated with unacceptable increased toxicity.