Red cells parasitized by Plasmodium knowlesi concentrate within the microcirculation of many organs including cerebral capillaries in rhesus monkeys. The possibility that P. knowlesi could alter the rheologic properties of red cells so that they are trapped within capillaries was investigated in the present study. The viscosity of P. knowlesi-infected red cells suspended in Ringer's solution was increased at all shear rates at hematocrits above 30%. At moderate parasitemia the resistance to flow through 5 mu polycarbonate sieves was increased; at high parasitemia the pores were obstructed. Mature trophozoites caused more obstruction than young trophozoites (rings) at any given level of parasitemia. The reduction of deformability of red cells infected by schizonts of P. knowlesi was further demonstrated by their exclusion from rouleaux in a plasma suspension. Therefore, the red cells infected by P. knowlesi become less deformable, and this reduction in red cell deformability may explain the obstruction of cerebral capillaries.