The nutrient Curcumin with anti-inflammatory and antitumor activity stimulates apoptosis of several nucleated cell types. The present study explored whether Curcumin similarly induces suicidal death of erythrocytes or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. PS exposing cells are phagocytosed and thus rapidly cleared from circulating blood. Erythrocyte membrane scrambling may be triggered by increase of cytosolic Ca2+ activity or formation of ceramide. To test for eryptosis, erythrocyte PS exposure was estimated from annexin V binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to Curcumin (± 1 mM) increased annexin V binding and decreased forward scatter, pointing to PS exposure and cell shrinkage. According to Fluo3 fluorescence Curcumin increased cytosolic Ca2+ activity and according to immunofluorescence it increased ceramide formation. As shown previously, hypertonic shock (addition of 550 mM sucrose), chloride removal and glucose depletion decreased the forward scatter and increased annexin V binding. The effects on annexin binding were enhanced in the presence of Curcumin. Exposure to Curcumin did, however, not significantly enhance the shrinking effect of hypertonic shock or Cl- removal and reversed the shrinking effect of glucose withdrawal. The present observations disclose a proeryptotic effect of Curcumin which may affect the life span of circulating erythrocytes.