Anti-A IgG antibodies have previously been shown to stimulate Ca2+ entry into erythrocytes which is known to trigger eryptosis, i.e. suicidal erythrocyte death, characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface. As macrophages are equipped with PS receptors, they bind, engulf and degrade PS exposing cells. The present experiments explored whether anti-A IgG triggers PS exposure of erythrocytes. PS exposure was estimated from annexin-V binding in FACS analysis. Exposure to anti-A IgGs (0.5 mg/ml) indeed significantly increased annexin binding in erythrocytes with blood group A, but not in those with blood group 0, an effect blunted by removal of extracellular Ca2+ . According to Fluo3 fluorescence, anti-A IgGs increased cytosolic free Ca2+ concentration. Whole-cell patch-clamp recordings revealed activation of Ca2+ -permeable cation channels following treatment with anti-A-IgGs. Ca2+ ionophore ionomycin triggered annexin binding and outward movement of the fluorescent PS analogue 1-oleoyl 2-[6-[(7-nitro- 2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-sn-glycero-3-phospho- L-serine (C6-NBD-PS). In conclusion, anti-A IgGs activate erythrocyte cation channels leading to Ca2+ entry and subsequent erythrocyte cell membrane scrambling. The effect most likely contributes to the elimination of erythrocytes following an immune reaction against the A antigen.