The course of malaria is not only a function of the parasite but similarly depends on properties of the host. Certain genetic defects, such as sickle cell trait, thalassemia and glucose-6-P- dehydrogenase deficiency confer some protection against a severe course of malaria. In all three diseases erythrocytes (RBCs) are more susceptible to eryptosis, a suidical death of RBCs characterized by phosphatidylserine (PS) exposure at the cell surface. PS exposing erythrocytes are engulfed, degraded and thus eliminated by macrophages. Accelerated eryptosis of infected cells may counteract the development of parasitemia during malaria. Recent observations disclosed the enhanced susceptibility of iron deficient RBCs to eryptosis. The present study thus explored whether iron deficiency influences the course of malaria and, if so, whether it is paralleled by accelerated clearance of infected RBCs from circulating blood. As a result, PS exposure was enhanced in Plasmodium falciparum infected human RBCs, an effect significantly more marked in iron deficiency. In mice, iron deficient RBCs were more rapidly cleared from circulating blood, an effect further accelerated by infection with P. berghei. Parasitemia in P. berghei infected mice was decreased and mouse survival significantly enhanced in iron deficiency. In conclusion, iron deficiency favorably influences the course of malaria, an effect presumably due to accelerated eryptosis and subsequent clearance of infected RBCs.