Plasmodiumfalciparum malaria parasites invade human erythrocytes by means of a parasite receptor for erythrocytes, the 175-kD erythrocyte binding antigen (EBA-175). Similar to invasion efficiency, binding requires N-acetylneuraminic acid (Neu5Ac) on human erythrocytes, specifically the glycophorins. EBA-175 bound to erythrocytes with receptor-like specificity and was saturable. The specificity of EBA-175 binding was studied to determine if its binding is influenced either by simple electrostatic interaction with the negatively charged Neu5Ac (on the erythrocyte surface); or if Neu5Ac indirectly affected the conformation of an unknown ligand, or if Neu5Ac itself in specific linkage and carbohydrate composition was the primary ligand for EBA175 as demonstrated for hemagglutinins of influenza viruses. Most Neu5Ac on human erythrocytes is linked to galactose by a2-3 and a2-6 linkages on glycophorin A. Soluble Neu5Ac by itself in solution did not competitively inhibit the binding of

F invasion of malaria parasites into human erythrocytes were prevented, the malaria life cycle would be interrupted and disease prevented. Thus, considerable effort has gone into understanding the molecular basis of parasite invasion into erythrocytes. Invasion requires recognition by the parasite of the appropriate host cell during one or more steps that include merozoite attachment, apical reorientation, apical junction formation, release of the contents of apical organelles, and entry into the erythrocyte (16, 21). The glycophorins, major sialoglycoproteins present on the erythrocyte surface, appear to be responsible for the sialic aciddependent invasion into erythrocytes by Plasmodium falciparum malaria merozoites (10, 11, 16, 18, 29, 30, 33-36). Recognition ofsialic acid-containing receptors on the erythro-