The Albert Mathieu Chorionepithelioma Registry's 1800 cases were screened, and 70 cases of trophoblastic disease involving the central nervous system were abstracted. In addition, eight patients with central nervous system trophoblastic disease from the Western Trophoblastic Disease Center, Department of Obstetrics and Gynecology, University of Southern California (USC) Medical Center, were reviewed. Eighteen patients received chemotherapy and whole-brain irradiation, 25 were treated with chemotherapy alone, and 35 received neither chemotherapy nor irradiation. In the no-treatment group (in which most patients died before therapy was begun), there were no survivors, and 74% of the deaths resulted from central nervous system causes. In the chemotherapy-alone group, 24% survived and 58% died of central nervous system causes. In the chemotherapy and irradiation group, 50% survived but none of the deaths were due to central nervous system involvement. This study suggests that radiation has a distinct therapeutic role in the treatment of central nervous system choriocarcinoma, and provides evidence that the irradiated brain tends to resist recurrent disease even in those patients for whom the outcome is fatal.