Hardening of the arteries has been repeatedly discussed in the literature for upward of three and a half centuries. It was noted by Amatus Lusitanus who made a study of the valves of blood vessels over seventy years before Willam Harvey brought forth his immortal work. More recently an immense amount of investigation has been done and a vast amount of literature has been published on the subject. However, although almost every conceivable phase of the problem has been studied, nevertheless there still remain to be demonstrated the underlying conditions which determine the development of atherosclerosis. Because it is so well known I shall not present any detailed description of the histology of atherosclerosis. However, I would like to emphasize one stage in its development, namely, that in which the earliest detectable changes appear. It is upon this that the subsequent alterations depend. As far as the causation of the disease is concerned it can be stated that those conditions which lead to the formati...