Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible.