Azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may accelerate clearance of Plasmodium-infected erythrocytes. The present study thus explored whether azathioprine influences eryptosis of Plasmodium-infected erythrocytes, development of parasitemia and thus the course of malaria. Phosphatidylserine-exposure was estimated from annexin V-binding and cell volume from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin V-binding and initially decreased forward scatter, effects significantly augmented by azathioprine. At higher concentrations azathioprine significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. Subcutaneous administration of azathioprine (5 mg/kg b.w.) significantly decreased the parasitemia of circulating erythrocytes and increased the survival of P. berghei-infected mice (from 0% to 80% 22 days after infection). In conclusion, azathioprine enhances suicidal death of infected erythrocytes, decreases parasitemia and fosters host survival during malaria.