We have examined the effect of chronic diabetes mellitus upon cell membrane composition and turnover in streptozotocin-treated rats and control animals maintained for four to eight weeks. Liver plasma membranes, prepared from diabetic animals, showed enhanced activities of alkaline phosphatase and glucose-6-phosphatase and depressed 5'-nucleotidase when compared with controls. Studies of the nonprotein constituents of liver plasma membranes and red cell “ghosts” showed similar changes in both tissues: sialic acid and cholesterol content were reduced in the membranes of diabetic animals, while phospholipids (total and individual classes) and neutral sugars were unchanged. To look for changes in relative turnover rates of individual membrane proteins, we combined a double-label in-vivo technic using [3H] and [14C] leucine with polyacrylamide gel separation of membrane proteins. No significant differences were observed between control and diabetic animals. In chronically diabetic animals, cell membranes may show significant changes in overall composition with no significant changes in the rate of protein turnover.