The classic sequence in the pathogenesis of osteoradionecrosis of the jaws has been accepted as radiation, trauma, and infection. This paper challenges this sequence and offers a new one more accurately describing the biochemical and cellular pathology. The clinical data are based on 26 consecutive cases of osteoradionecrosis from which 12 en bloc resection specimens were cultured and stained for microorganisms. Review of the histories and treatments, as well as the microbial assays, indicates that microorganisms play only a contaminant role in osteoradionecrosis and that trauma is only one mechanism of tissue breakdown leading to the condition. The sequence suggested by this study is as follows: (1) radiation, (2) hypoxic-hypocellular-hypovascular tissue, (3) tissue breakdown, and (4) chronic non-healing wound.