cells without the differentiation of undegenerated cells. These various expressions of opinion would justify the conclusion that with the onset of old age the degenerative processes in the cells lead to the production of less specialized cells which have the compensating property of more vigorous growth, and that in certain circumstances, one of which is very probably a diminished power of resistance on the part of the surrounding tissues and another, and very important one, irritation in some form or another, riotous proliferation of the cells invades the adjacent parts. That the conditions necessary are usually local is strongly suggested by the appearance of the new growth at one spot only and by the frequent absence of recurrence after free removal. There may be a premature local senescence of the tissues, just as there is premature old age of the body generally, and this would explain the exceptional occurrence of malignant disease in early life or long before the usual time. VI NORMAL STRUCTURAL CHANGES IN OLD AGE Physiological old age, namely a process of involution and atrophy uncomplicated by superimposed pathological changes, is extremely rare; pathological processes may initiate and hurry on a condition imitating old age, and indeed the morbid changes found after death in old people commonly show the lesions of past infections in addition to those of physiological involution, and the longer life lasts the greater the probability that changes due to disease will accumulate. It is therefore difficult to determine accurately where physiological involution ends and pathological lesions begin, and there has been much confusion between physiological old age and pathological senility. It must, on the other hand, be admitted that the ideal condition of physiological involution without some definite evidence of superadded pathological change hardly ever comes before us. In fact at the best old age is almost always but relatively physiological, in other words, as Metchnikoff wrote in 1903, there is at present, from the conditions of inharmonious environment, no chance of a really physiological old age and death for mankind. But the view that old age is invariably the accumulated product of multiple injuries due to infection and poisons, or that it is due to arteriosclerosis (Boerhaave, Haller, Demange) is an entirely different proposition and does not fit in with biological knowledge. While fully recognizing the difficulties an attempt may be made to tabulate the natural changes accompanying and responsible for old age, and to contrast them with the pathological changes commonly complicating the normal structural involution of the human body.