Acute and chronic morphologic changes in the endothelium and the media of canine femoral arteries following 4,000 roentgen given over a ten day period were evaluated by light and scanning electron microscopy. The endothelium showed evidence of moderate to severe acute injury within 48 hours after the course of radiation was completed, as evidenced by marked nuclear disruption with sloughing of entire cells in some areas and widespread patchy intimal fibrin deposition. Repopulation of the luminal surface with new cells forming an irregular and thickened surface became apparent within three weeks but was still incomplete at four months. The internal elastic membrane appeared to be preserved following radiation. The media evidenced minimal alteration during the first week subsequent to radiation, after which a progressive increase in cellularity and later fibrosis with some focal areas of necrosis and round cell infiltration occurred. The adventitia showed progressive hemorrhage and chronic inflammation. The results of this study suggest that radiation injury to the endothelium may be independent from injury to the remainder of the wall of the vessel. The morphologic alterations in the media and adventitia may be long lasting and perhaps permanent in contrast to the more acute changes with gradual repair in the endothelium. Arterial thrombosis is uncommon following radiation.