Human erythrocytes express non-selective cation (NSC) channels which are activated by prostaglandin E2 (PGE2) or by Cl- removal. Activation of NSC channels triggers suicidal erythrocyte death (eryptosis) which is characterized by Ca2+ -stimulated cell shrinkage and phosphatidylserine (PS) exposure. In addition, the intraerythrocytic malaria parasite Plasmodium falciparum activates the NSC channels most probably to accomplish Na+ and Ca2+ entry into the erythrocyte cytosol needed for parasite development. Flufenamic acid has previously been shown to inhibit NSC channels. The present study thus explored the effect of flufenamic acid on suicidal erythrocyte death and on intraerythrocytic parasite growth. Within 48 hours replacement of extracellular Cl- with gluconate or application of PGE2 (50 mM) increased Fluo3 fluorescence reflecting cytosolic free Ca2+ concentration, decreased forward scatter in FACS analysis reflecting cell volume and increased annexin V binding in FACS analysis reflecting PS exposure. All those effects were significantly blunted in the presence of flufenamic acid (10 mM). Flufenamic acid (25 mM) further delayed significantly the intraerythrocytic growth of P. falciparum and the PS exposure of the infected erythrocytes. The present observations disclose a novel effect of flufenamic acid, which may allow the pharmacological manipulation of erythrocyte survival and the course of malaria.