The majority of children with brain stem gliomas develop progressive disease within 18 months of diagnosis and treatment. Radiotherapy (RT) is of transient benefit in most patients and higher total doses of RT have been related to improved survival. The amount of RT which can be given is limited by the tolerance of the surrounding brain. Hyperfractionated RT theoretically allows higher doses of RT to be tolerated by the brain. Sixteen children with brain stem gliomas were treated on a hyperfractionated RT schedule, receiving 120 cGy of RT twice daily, to a total dose of 6480 cGy. All patients tolerated treatment well. Eleven of 15 (73%) evaluable patients had a response to treatment and two (13%) others had stable disease. One patient developed progressive disease during treatment. All patients were tapered off steroids by the completion of treatment. Thirteen of 16 (81%) patients developed progressive disease at a median of 7 months after diagnosis and three remain in remission 8, 12, and 15 months following diagnosis. These results were similar to those of historical controls. Two patients were surgically explored at time of relapse and 5 have had an autopsy. No acute or subacute neurologic toxicity was seen; but long-term detrimental effects on brain could not be assessed. The implications of this study are that escalations of the dose of hyperfractionated RT can be entertained for children with brain stem gliomas.