Changes occurring in membrane saccharides during the in vivo aging of normal human erythrocytes have been evaluated after the fractionation of the red cells into five age groups by density gradient centrifugation. The glycoconjugate fractions studied included sialoglycoproteins, macroglycolipids, low-molecular-weight glycolipids, and Band 3 glycoproteins. All of the carbohydrate constituents of the membrane were found to decrease relative to the total ghost protein as a function of cell age, with the most substantial losses occurring in the macroglycolipids (50%) and Band 3 glycoprotein (30%); the smallest changes were observed in the sialoglycoproteins (13%). No preferential loss of sialic acid or other peripheral sugars was found, making unlikely the importance of glycosidase action in the removal of sugars from the membrane. It is suggested that the changes observed in the composition of the ghosts during aging are best explained by a loss of membrane segments enriched in glycoproteins and glycolipids and deficient in internally located molecules such as spectrin. Analyses were also performed on the glycoconjugate fractions from diabetic erythrocytes separated according to cell age. These erythrocytes, which had glycosylated hemoglobin values twice those of normals, had somewhat smaller amounts of membrane-bound carbohydrate. The difference between diabetic and normal erythrocytes was greatest when young cells were examined (diabetic to normal = 0.93), suggesting that the known increased turnover of red cells in diabetes leads to an early loss of membrane constituents.