Central nervous system (CNS) involvement was evaluated in 277 consecutive patients with aggressive non-Hodgkin's lymphoma treated by the Nebraska Lymphoma Study Group. Three patients (1.1%) developed CNS involvement at presentation and 11 (4.0%) at relapse. The involvement was meningeal in 8 patients and documented by CSF cytology; it was parenchymal in 2 patients and proven by biopsy; and it was in the cauda equina in 1 patient at autopsy. Factors significantly associated with a greater likelihood of CNS relapse were age less than 60 years and epidural disease. Other factors, including tumor histology, extranodal disease at presentation, response to therapy, sex, and symptom type, were not significantly associated with a higher risk of CNS relapse. Survival of the patients presenting with CNS disease (6, 26, and 27+ months) was longer than patients whose CNS disease relapsed (median 2 months).