Intraoperative radiation therapy (IORT) and interstitial radiotherapy (brachytherapy) are highly effective adjunctive treatments for head and neck cancer. The radiotolerance of the carotid artery, pharynx, and mandible to therapeutic doses of these modalities, however, has not been clearly established. To investigate the effects of IORT and interstitial iridium 192 (192Ir) on these structures in the canine, both sides of the neck of 12 mongrel dogs were operated on to expose 4-cm segments of the common carotid artery, pharynx, and mandible. One side of the neck was irradiated in each animal with the opposite side serving as the unirradiated control. The animals were divided into 3 groups of 4 dogs each. The first group received 40-Gy IORT and the second, 60-Gy IORT. In the third group of animals, afterloading catheters were implanted followed by placement of 60-Gy 192Ir. At 2 and 4 months after irradiation, 2 dogs in each treatment group were killed and histopathologic examination of the carotid artery, pharynx, and mandible was performed using hematoxylin-eosin staining. No statistically significant difference between treatment groups was found for carotid artery injury, but a trend for the proportion of fibrosis of the carotid on the irradiated side to increase with dose (P = .125) and time (P = .250) was noted. No apparent or statistically significant difference was found between treatment groups for pharyngeal injury. The greatest histologic changes noted following IORT and 192Ir brachytherapy were found in mandible specimens. The incidence of bone marrow suppression in irradiated mandible specimens versus controls approached statistical significance (P = .062). Osteoradionecrosis (ORN) was noted in the irradiated mandible specimens of two dogs, one of which received 60-Gy IORT and the other 60-Gy interstitial 192Ir. This manuscript reviews animal and clinical investigations relevant to the use of IORT and interstitial radiotherapy to the head and neck. Recommendations are made regarding further animal and clinical research as well as methods of treatment.