Sialic acid (SA) content and Na+/K+-ATPase activity of red blood cell (RBC) membranes were studied in 26 normoalbuminuric patients with insulin-dependent diabetes mellitus (IDDM), 25 normoalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM), and 40 healthy nondiabetic subjects with a negative family history for diabetes. A decrease in RBC membrane SA content and Na+/K+-ATPase activity was observed in older control subjects compared with younger controls. A significant correlation between age, Na+/K+-ATPase activity, and SA content was also found. No difference was observed in RBC membrane SA content between IDDM and NIDDM subjects, but Na+/K+-ATPase activity was significantly lower in IDDM patients. SA content was increased in NIDDM subjects compared with healthy subjects of similar age, whereas Na+/K+-ATPase activity was significantly lower in both IDDM and NIDDM subjects compared with controls. In NIDDM, Na+/K+-ATPase activity was significantly correlated with age, whereas both Na+/K+-ATPase activity and SA content were significantly correlated in IDDM and NIDDM patients. Hemoglobin A1c, (HbA1c) levels did not show any significant correlation either with Na+/K+-ATPase or with SA content in diabetic patients. The modified SA content and Na+/K+-ATPase activity in elderly subjects described in the present study indicate a similar behavior of the erythrocyte membrane during both RBC senescence and aging of subjects.