Eryptosis or apoptosis-like death of erythrocytes is characterized by phosphatidylserine exposure and erythrocyte shrinkage, both typical features of nucleated apoptotic cells. Eryptosis is triggered by activation of non-selective Ca²⁺-permeable cation channels with subsequent entry of Ca²⁺ and stimulation of Ca²⁺-sensitive scrambling of the cell membrane. The channels are activated and thus eryptosis triggered by Cl^-- removal, osmotic shock, oxidative stress or glucose deprivation. The present study has been performed to compare cation channel activity and susceptibility to eryptosis in neonatal and adult erythrocytes. Channel activity was determined utilizing patch clamp, cytosolic Ca²⁺ activity by Fluo3 fluorescence, phosphatidylserine exposure by FITC-labelled annexin-V binding, and cell shrinkage by decrease of forward scatter in FACS analysis. PGE₂ formation, cation channel activity, Ca²⁺ entry, annexin-V binding and decrease of forward scatter were triggered by removal of Cl^- in both, adult and neonatal erythrocytes. The effects were, however, significantly blunted in neonatal erythrocytes. Osmotic shock, PGE₂ and PAF similarly increased annexin V binding and decreased forward scatter, effects again significantly reduced in neonatal erythrocytes. On the other hand, spontaneous and oxidative stress (addition of tert-butylperoxide)-induced eryptosis was significantly larger in neonatal erythrocytes. In conclusion, cation channel activity, Ca²⁺ leak and thus channel-dependent triggering of eryptosis are blunted, whereas spontaneous and oxidative stress-induced eryptosis is more pronounced in neonatal erythrocytes.