Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.