To extend previous studies on the apparent acceleration of collagen aging in diabetes mellitus, dura collagen from human adults of different ages, with and without diabetes, was processed to yield soluble and insoluble fractions. Insoluble fractions were cleaved by cyanogen bromide. Release of peptides from insoluble collagen by cyanogen bromide decreased markedly with age and was much less from the collagen of diabetics than from nondiabetics of similar ages. The acrylamide gel profiles of peptides released were similar, but not identical, for samples of different ages and for samples from diabetics. It was concluded that age-dependent and diabetes-dependent cross-linking was widespread throughout helical regions of collagen molecules and that collagen throughout the body is altered in diabetes. Analyses of fragments of insoluble collagen are required to gain information on the chemistry of the cross-links that form with aging and diabetes.