Observations indicating an enhancing effect of sodium on hemolysis of red cells suspended in dextrose solution prompted study of the mechanism of this effect. Osmotic fragility of red cells from normal subjects and from patients was measured in 5% dextrose solution (5D/W), 5% dextrose combined with various concentrations of sodium chloride (5D/NaCI), lithium chloride, and potassium chloride. The influence of ouabain on osmotic hemolysis in 5D/ NaCl was also studied, and the glucose content of ghost red cells was determined whenincubated in 5% dextrose with 0.0570 NaCl(SD/O.OSNaCl), as compared with W j W .In the presence of minimal amounts of NaCl(O.O5%) at pH 4.8, average hemolysis was greater than in the absence of NaC1, ie, 39% vs 24% in normal subjects (P < 0.02) and 4070 vs 3 1% in a group of unselected patients (P < 0.05). When the pH was adjusted to 7.4 in the patient group, the results were 34% vs 21% ( P < 0.05). The sodium-induced enhancement of hemolysis in dextrose solution was virtually duplicated when LiCl and KC1 were substituted for NaCl (P < 0.01 and < 0.05, respectively). On the other hand, in the presence of ouabain, the sodium-induced enhancement of hemolysis was abolished. The overall glucose content of ghost red cells incubated in 5D/ O.OSNaC1 was 53% greater than in 5D/W (P < 0.005), whereas with ghost red cells depleted of adenosine triphosphate (ATP), it was only 32% greater (P < 0.0 1). is enhanced by the sodium ion, presumably by triggering the membrane sodium-potassium ATPase system. These results suggest that glucose transport across the red cell membrane