The mechanisms underlying splenic host defence in malaria have not been precisely defined but they include both immunological and non-immunological interactions with parasitized erythrocytes. Studies of the intravascular clearance of 51Cr-labelled Plasmodium berghei-infected erythrocytes in the rat show that these cells are cleared predominantly by the spleen, and to a greater extent in immune than non-immune animals. Transfer of hyperimmune rat serum imparted protection to challenge with P. berghei-infected red cells but did not alter the magnitude or rate of clearance of the infected cells. Rising parasitaemia during acute infection was associated with diminished splenic clearance of the infected cells as well as of rigid, uninfected red cells (heated or Heinz body-containing). Just before the onset of spontaneous resolution (crisis) a marked increase in splenic clearance was observed. These changes could be related to alterations in the splenic microcirculation. From these studies it is concluded that opsonization of P. berghei-infected erythrocytes is not an important mechanism of protection in the rat. Rather, the altered rheological properties of these cells may result in their trapping within the spleen. Presumably, these rheological changes occur in malarias caused by different Plasmodium species. On the other hand, opsonization of parasitized erythrocytes, although not found in rodent malaria, might yet prove to be an important defence mechanism in primate malaria.