Apigenin, a flavone in fruits and vegetables, stimulates apoptosis and thus counteracts cancerogenesis. Erythrocytes may similarly undergo suicidal cell death or eryptosis, characterized by cell shrinkage and phosphatidylserine-exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide-formation and ATP-depletion. The present study explored the effect of apigenin on eryptosis. [Ca²⁺]_i was estimated from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, ceramide utilizing antibodies, and cytosolic ATP with luciferin-luciferase. A 48 h exposure to apigenin significantly increased [Ca²⁺]_i (>=1mM), increased ceramide-formation (15mM), decreased ATP-concentration (15mM), decreased forward scatter (>=1mM), increased annexin-V-binding (>=5mM) but did not significantly modify hemolysis. The effect of 15mM apigenin on annexin-V-binding was blunted by Ca²⁺-removal. The present observations reveal novel effects of apigenin, i.e. stimulation of Ca²⁺-entry, ceramide-formation and ATP-depletion in erythrocytes with subsequent triggering of suicidal erythrocyte death, paralleled by cell shrinkage and phosphatidylserine-exposure.