As the head and neck surgeon expands the boundaries of resectability into the skull base, the margin of tumor clearance diminishes. Intraoperative radiotherapy (IORT) can be used as an adjunct to skull base surgery and external beam radiation to enhance local control in areas with close margins or remaining microscopic disease. During the period from May 1982 to May 1988, 25 patients underwent IORT of the skull base following resection and prior to closure to treat microscopic disease in 9 patients, sterilize close margins in 14 patients, and attempt to eliminate remaining gross disease in 2 patients. The types of tumors treated were 13 squamous cell carcinomas, 4 adenoid cystic carcinomas, 3 high-grade mucoepidermoid carcinomas, 3 sarcomas, 1 malignant mixed tumor, and an oncocytic adenocarcinoma. The majority of the tumors either originated in the sinuses or were skull base extensions of oral cavity or oropharyngeal cancers. In 22 patients with 1-year follow-up, IORT prevented local recurrence in 14 (64%) patients. This may represent improved control of local disease in patients who historically have a very dismal prognosis. The indications, techniques, and complications of this exciting therapeutic modality are also reviewed.