The distribution in organs and the ultrastructure of red cells of Macaca mulatta parasitized with Plasmodium knowlesi were compared with results of previous studies with Plasmodium falciparum and Plasmodium coatneyi. Schizonts of P. knowlesi were more numerous in the peripheral blood, especially at high parasitemia, than in the other two malaria infections. At low parasitemia, schizonts of P. knowlesi were trapped principally in the periportal hepatic sinusoids and in the submucosal venules of small intestine. As parasitemia increased, parasitized red cells were concentrated in other organs, many cerebral capillaries and venules being filled by them. Red cells infected with P. falciparum and P. coatneyi disappeared from the peripheral circulation as the parasites matured (deep vascular schizogony) and were trapped in the heart, adipose tissue, and, to a lesser extent, in other organs. In both infections, knob-like protrusions on the red cell membrane were seen by electronmicroscopy. The absence of cerebral sequestration in P. falciparum and P. coatneyi at low parasitemia may reflect the efficiency with which their schizonts were removed at other sites. An occasional electron-dense invagination of plasma membrane of red cells infected with P. knowlesi was observed by electronmicroscopy; no knob-like protrusions were seen. We conclude that the mechanism for deep, vascular schizogony in P. knowlesi differs from that in P. falciparum and P. coatneyi.