The Ring-Infected Erythrocyte Surface Antigen (Pf155/RESA) sequence was chemically synthesized: in fifty four 20-mer sequential peptides, covering the entire protein, each of which was tested in erythrocyte binding assays. Peptides 6671 and 6673, corresponding to residues 141-160 and 181-200, respectively, presented a high specific binding activity to erythrocytes with affinity constants of 190 nM and 105 nM respectively. Their binding was sensitive to previous enzymatic treatment of erythrocytes. A region of peptide 6673 has been identified, very recently, as a B-cell epitope, target of neutralizing antibodies (Siddique AB, Iqbal J, Ahlborg N, Wahlin FB, Perlmann P, Berzins K. Antibodies to nonrepeat sequences Of antigen Pf155/ RESA of Plasmodium falciparum inhibit parasite growth in vitro. Parasitol Res 1998;84:485-91). The critical residues for erythrocyte binding for peptide 6671 (MTDVNR YR YSNNYEAIPHIS) and for peptide 6673 (LGRSGGDI/KKMQTLWDEIM) were recognized. Based on these data, the presence of five functional regions of RESA is postulated. (C) 2000 Elsevier Science Ltd. All rights reserved.