Erythrocytes infected with the human malaria parasite become structurally and antigenivally modified as a consequence of intracellular parasite development. The new antigens that appear on the surface of the infected enthrocyte originate from parasite-encoded proteins and by modification of the erythrocyte membrane protein band 3, Here, we show that anti-peptide antibodies generated against an amino acid sequence (YETFSKLIKIFQDH) of human hand 3, and previously identified as mediating adhesion or infected erythrocytes to CD36, recognized P. falciparum-infected erythrocytes. In addition. Sera from individuals living in a malaria endemic area (and who are presumably immune) contained immunoglobulins specific for this region of band 3, The anti-peptide antibodies reacted with the falciparum-infected erythrocytes. In uninfected erythrocytes, the band 3 region was cryptic and its exposure surface excrescences (knobs) on falciparum-infected erythrocyte surface required clustering of band 3 protein, Thus, a parasite-induced modification of band 3 promotes adhesion and induces antigenic changes in the P falciparum-infected erythrocyte, (c) 2005 Elsevier B.V.. All rights reserved.