The gross and microscopic changes as well as the biochemical alterations in the mucopolysaccharides and collagen of the aorta were studied in male albino rabbits exposed to systemic hypoxia. The hypoxia was produced by nitrogen breathing until unconsciousness and convulsions were produced and was performed four times daily for 2 weeks. Of 19 animals thus treated, 15 showed gross arteriosclerotic changes in the aorta. Simultaneously, an increase in the aortic content of acid mucopolysaccharides, in the synthesis of sulfomucopolysaccharides and in the content of collagen were observed. The biochemical changes were interpreted as processes of repair elicited by injury to the aortic wall. The general hypoxia was accompanied by an increase in the arterial blood pressure and dilation of the aorta, most marked in the thoracic part, which also was the site of the most severe gross changes. The arteriosclerotic changes were probably caused by a mechanical as well as a hypoxic injury to the aortic wall. © 1969, Sage Publications. All rights reserved.