Although the precise pathogenic mechanisms are not fully understood, osteoradionecrosis of the mandible is caused by radiation-induced cellular injury, ultimately resulting in a chronic, nonhealing wound. This etiology does not explain the strong predisposition of the mandible to radionecrosis relative to the maxilla, and overlooks the contribution of ischemic necrosis due to radiation-induced disturbances in circulation. In this study, irradiated mandibles with and without osteoradionecrosis and nonirradiated mandibles were examined histologically. Our findings show that osteoradionecrosis of the mandible is an ischemic necrosis due to radiation-induced obliteration of the inferior alveolar artery, while revascularization by branches of the facial artery is disturbed by radiation-induced vascular disease and periosteal damage. The most vulnerable part of the mandible is the buccal cortex of the premolar, molar, and retromolar regions.