Stereotactic brain biopsy was used to establish diagnoses of conditions in patients with AIDS. Two hundred fifty stereotactic biopsies and one open resection were performed for 243 patients. Pathologically abnormal tissue was obtained in 246 (98%) of the procedures, and 16 patients (6%) had >1 diagnosis. Diagnoses included lymphoma in 82 (33%), progressive multifocal leukoencephalopathy in 73 (30%), and tumors not ordinarily associated with AIDS in 7 (3%). In one-third of the cases, the tissue diagnosis differed from the predicted diagnosis. Four of the first 32 patients (12%) developed intracranial bleeding hours after surgery, which was fatal in 3 (9%). Subsequently, all patients were treated with a coagulopathy protocol that included preoperative and postoperative administration of coagulation factors, and there were no further instances of delayed bleeding in the 218 subsequent patients. Among those later patients, there were 7 complications (3%), leading to 4 deaths (2%), a complication rate that compares favorably with that among patients without AIDS.