The manner in which the malarial parasite, Plasmodium falciparum, invades and destroys human red cells is uncertain. Surface and internal anatomy of erythrocytes from subjects with parasitemia was examined in an effort to understand this process better. P. falciparum causes marked distortion of the surface of red cells. In parasitized cells, the bulk of the organism lies under a smooth erythrocyte exterior, but part of it is often associated with a highly irregular red cell surface defect. Many cells without parasites have cavitary surface defects. Their appearance suggests that they previously may have contained parasites. These morphologic observations offer possible explanations for premature destruction of parasitized as well as nonparasitized red cells.