Eryptosis or apoptosis-like death of erythrocytes is characterized by phosphatidylserine exposure and erythrocyte shrinkage. Eryptosis is triggered by activation of non-selective Ca2+-permeable cation channels with subsequent entry of Ca2+ and stimulation of a Ca2+-sensitive scramblase. The channels are activated and thus eryptosis triggered by Cl- removal or osmotic shock. The present study has been performed to elucidate the cation channel activity of fetal erythrocytes, and to compare their susceptibility to eryptosis with the susceptibility of adult erythrocytes. Cation channel activity, Ca2+ entry, annexin binding and decrease of forward scatter were triggered by removal of Cl- in both, adult and fetal erythrocytes. The effects on fetal erythrocytes, however, were significantly blunted. Osmotic shock similarly increased annexin binding and decreased forward scatter, effects again significantly reduced in fetal erythrocytes. On the other hand, spontaneous eryptosis was slightly but significantly larger in fetal erythrocytes. In conclusion, cation channel activity, Ca2+ leak and thus channel-dependent triggering of eryptosis are blunted in fetal erythrocytes, whereas spontaneous eryptosis is more pronounced in those erythrocytes.