Preirradiation chemotherapy is a potentially important component of combined treatment for brain tumors; however, concerns over its side effects and antitumor activity have impeded its evaluation in clinical trials. To determine the feasibility of administering such therapy to children, we assessed the responses of 38 brain tumor patients (median age, 2 years) to 12 weeks of combination chemotherapy given after surgical resection but before irradiation. Transient myelosuppression was noted in all patients, but was not associated with infections or complications of surgical wounds. The ability of the patients to perform activities of daily life, as rated with the Karnofsky performance scale, was either improved (n = 14) or unchanged (n = 18) at the end of the evaluation period. In the remainder of the group, functional deterioration was clearly related to causes other than drug treatment. Prior chemotherapy did not compromise the delivery of radiation except for a brief interruption of spinal irradiation in 3 patients. Objective responses to chemotherapy, defined as a greater than 50% decrease in tumor masses, occurred in 16 of the 31 patients who had subtotal resections; only 6 patients in the entire group showed disease progression during the 12 weeks of drug administration. We conclude that chemotherapy of the type used in this study is well tolerated and produces beneficial effects in children with brain tumors.