The 175kD Plasmodium falciparum erythrocyte binding antigen (EBA-175) is localized in micronemes at the apical end of merozoites and binds sialic acid residues on glycophorin A on red cells to mediate invasion [1, 2]. The extracellular region of EBA-175 contains two conserved, cysteine-rich regions, regions II and VI, that share sequence homology with members of the erythrocyte binding protein family (EBP family), which includesP. vivaxandP. knowlesiDuffy binding proteins (PvDBP and PkDBP) and P. falciparum erythrocyte binding proteins EBA-140, EBA-181 and EBL-1 [3–5]. The N-terminal, conserved, cysteine-rich domain of EBA-175, region II, contains tandemly repeated cysteine-rich domains, F1 and F2, which are also referred to as Duffy-binding-like (DBL) domains because they share homology with receptor-binding domains of PvDBP and PkDBP that bind the Duffy blood group antigen [6, 7]. The receptor-binding domain of EBA-175 has been mapped to region F2, which binds sialic acid residues on glycophorin A with specificity [1, 8]. Antibodies raised against recombinant F2 have been shown to block red cell invasion by P. falciparum in vitro providing support for the development of a recombinant malaria vaccine based on this functional domain [9]. Here, we investigate the extent of sequence diversity found in region F2 of EBA-175 in Indian P. falciparum field isolates. In addition, we test the ability of antibodies raised against the vaccine construct based on recombinant F2 from the P. falciparum Malayan Camp strain EBA-175 to inhibit red cell binding by F2 variants derived from diverse field isolates.