Natural IgG antibodies to band 3 glycoprotein of erythrocyte membrane (anti-band 3 IgG) are known to bind to senescent erythrocytes, and believed to initiate antibody-dependent phagocytic removal of the senescent cells from blood circulation. Anti-band 3 antibodies also bind to the erythrocytes with hereditary hemoglobin abnormalities such as sickle, beta-thalassemic and hemoglobin Köln erythrocytes. Oxidative stress appears to be responsible for the generation of senescent cell antigen on erythrocytes, to which anti-band 3 antibodies bind, since erythrocytes oxidized in vitro bind anti-band 3 IgG, and various oxidative modifications are observed in senescent erythrocytes as well as the erythrocytes with abnormal hemoglobin. Major antigenic sites of band 3 for anti-band 3 IgG autoantibodies are its sialylated poly-N-acetyllactosaminyl saccharide chains. The poly-N-acetyllactosaminyl saccharide chains on senescent erythrocytes are indeed involved in the antigenic sites on senescent erythrocytes. The finding of the carbohydrate epitopes and possible involvement of oxidative mechanism are compatible with the band 3 clustering hypothesis, in which clustering of band 3 molecules in erythrocyte membrane is supposed to be responsible for effective binding of anti-band 3 IgG to the cell surface, because the carbohydrate epitopes of band 3 can form multivalent epitopes on cell surface when band 3 molecules cluster, and oxidative stress can induce such clusters. Interestingly, poly-N-acetyllactosaminyl chains of band 3 on oxidized erythrocytes are also recognized by macrophages directly. Thus, poly-N-acetyllactosaminyl chains may play dual roles as determinants for recognition by anti-band 3 IgG and by macrophages.