Erythrocytes from pigs with experimental porcine eperythrozoonosis were examined using light microscopy and scanning and transmission electron microscopy. Three distinct forms of Eperythrozoon suis were attached to the plasma surface of erythrocyte membrane. Erythrocytes were initially parasitized by one or several immature forms. Immature forms enlarged and developed into juvenile and mature forms. The parasite replicated by budding of small immature forms from larger immature forms, juvenile forms, and mature forms. Small immature forms attached to adjacent membrane of the same erythrocyte or a nonparasitized erythrocyte. E. suis organisms were intimately associated with, but distinctly separated from erythrocyte membrane by a 30-nm electron lucent zone. Cell membrane in this area was denser than adjacent nonparasitized membrane. Early interaction between erythrocyte membrane and small immature forms resulted in no membrane deformation, but as this form enlarged, it later became embedded in a deep cup-like membrane invagination. As the immature form developed into the juvenile form a shallow, broad-based depression was observed in the membrane. A similar depression that covered a greater surface area was observed in the membrane parasitized by the mature form. The interaction between the parasitic forms and erythrocyte membrane resulted ultimately in severe membrane deformation. Parasite-membrane interactions may play an important role in the development of misdirected immune responses in experimental porcine eperythrozoonosis.