Abstract OBJECTIVE: The benefits of radiation therapy are generally denied to infants with malignant brain tumors because of the risk of devastating cognitive decline. Efforts to limit this morbidity with radiosurgical techniques have not been feasible for infants because of the dual requirements of rigid head fixation and high precision. We report the radiosurgical treatment of five infants by use of a robotically controlled system without rigid head fixation. METHODS: Five infants with malignant brain tumors received radiosurgical treatment with a robotically driven linear accelerator. Immobilization was aided by general anesthesia, form-fitting head supports, face masks, and body molds. The average marginal dose was 17 ± 2 Gy, and the average treatment volume was 18 ± 22 ml. RESULTS: X-rays obtained during treatment revealed acceptable agreement with preoperative computed tomographic scans in all patients. In one patient, the lesion did not progress, but a distant recurrence occurred 15 months after radiosurgery and also was treated with radiosurgery. In another patient, tumor in the treated region did not progress, but recurrence elsewhere led to death 7 months after treatment. Tumor enlargement occurred in Patient 3 at 3 months posttreatment, leading to death 2 months later. Tumor size was smaller in the remaining two patients at 9 and 11 months after treatment. There has been no toxicity attributed to treatment. CONCLUSION: Radiosurgery with minimal toxicity can be delivered to infants by use of a robotically controlled system that does not require rigid fixation. A formal dose-escalation trial is under way to address dose and toxicity for infants more thoroughly.