The major changes associated with the degeneration of human joints occur in the articular cartilage. However, the distinction between the degenerative process and the normal aging process has not been made definitively. Recent articles have emphasized the histologic aspects of the degenerative changes, but these same changes have not been studied histochemically. There have been some biochemical studies on human costal cartilage, but this cartilage was obtained at autopsy. Iob and Swanson (1) in 1937, working with fetal epiphyseal and costal cartilage, determined the extracellular and intracellular water by means of electrolyte studies. Their material was obtained at autopsy, eight to sixteen hours after death. Hagerty et al.(2) in 1960, using human costal cartilage from "fresh cadavers," carried out histologic examinations and studies of metabolism and water and electrolyte exchanges. Our present study is an attempt to record the histochemical changes which occur within normal human cartilage as a result of aging.Acquisition of normal human articular cartilage proved to be difficult. Tissue obtained at autopsy could not be used because of the electrolyte shifts that take place during and following death. We therefore found it necessary to use cartilage from surgical specimens. However, if the surgical operation was being performed for disease or degeneration of the joint, the cartilage of that joint could not be regarded as normal. It was necessary to rely upon cartilage removed from joints not affected by disease or degeneration. Our major source of cartilage was from amputation specimens. For example, if the amputation had been performed to remove a malignant lesion involving the proximal femur, then the articular surfaces of the knee and foot might be normal. However, even in these instances, 1 2 J. S. MILES AND L. EICHELBERGERVol. X I I if the patient had experienced prolonged disability as a result of sarcoma, the cartilage would show evidence of atrophy and could not be considered normal.Other abnormalities also necessitated the discarding of specimens, e.g., significant degenerative arthritis or disease demonstrated roentgenographically, microscopically, or on gross examination. Thus many factors were considered before the cartilage specimen was accepted. These decisions had to be made with uniformit'y, and therefore were made each time by JSM, although the specimens were obtained from the clinics at both the University of Colorado and the University of Chicago.The cartilage accepted for this study was handled in a manner identical with that described in previous papers (3-5). In most instances the amount of material from a single joint was sufficient for the analyses. There was no combining of cartilage from different joints, except from those of the foot; in the foot, the amount of cartilage provided by one intertarsal joint was so small that all the material obtained from these joints was combined for analyses. The dry samples were ground to a fine powder as previously described (6).The analyses of the...