Malaria, a disease accounting for more than one million deaths per year, is caused by intraerythrocytic growth of Plasmodia. Parasitemia may be blunted by suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine exposure. Triggers of eryptosis include lead nitrate (Pb(NO3)(2)). As shown here, Pb(NO3)(2) (>= 10 mu m) increased phosphatidylserine exposure of Plasmodium falciparum-infected human erythrocytes, an effect significantly more marked than in noninfected cells. Pb(NO3)(2) treatment accelerated the clearance of erythrocytes from circulating blood. Parasitemia in Plasmodium berghei-infected mice was significantly decreased and mouse survival significantly enhanced by 100 mu M Pb(NO3)(2) (20 ppm) in drinking water. The treatment significantly increased reticulocyte number but did not significantly decrease erythrocyte number in noninfected mice and in infected animals mainly triggered the disappearance of P. berghei harbouring erythrocytes. In conclusion, Pb(NO3)(2) accelerates eryptosis and subsequent clearance of infected erythrocytes and thus favourably influences the course of malaria. (C) 2007 Elsevier Inc. All rights reserved.