The solubility of collagen from human skin, tracheal cartilage and dura mater was compared. Skin contained the greatest amount of soluble collagen followed by dura and cartilage. An age-related decrease in the proportion of neutral salt-soluble collagen was observed for cartilage and dura. The proportion of collagen soluble in acetic acid decreased as a function of age in skin and dura. An age-related decrease in the proportion of skin and dura collagen released by pepsin digestion was also observed, as was a concomitant increase in the proportion of insoluble collagen in these tissues. Individuals with juvenile onset diabetes had significantly less salt-soluble dura collagen, acid-soluble skin and dura collagen, pepsin-released skin and dura collagen, and significantly more insoluble skin and dura collagen than comparably aged nondiabetics. One young maturity onset diabetic had significantly less salt-soluble dura collagen, pepsin-released skin and dura collagen, and significantly more insoluble skin and dura collagen than similarly aged non-diabetics. The solubility of collagen from tissues of older maturity onset diabetics, however, did not differ significantly from other old nondiabetics. These data indicate that there is a direct effect of age on the solubility of collagen from human tissues, and that based on solubility, cartilage collagen ages faster than dura collagen, with skin undergoing the slowest relative aging. These data also support previous observations indicating that collagen from individuals with diabetes mellitus undergoes accelerated aging. Alterations in collagen may be responsible for some of the debilities of age that occur in collagen-rich tissues, and which appear at an earlier age and more severely in individuals with diabetes mellitus.