A genomic DNA fragment that encodes a Plasmodium falciparum antigen has been isolated by using human antibodies eluted from the membrane of infected erythrocytes. The antigen has a very unusual primary structure; it is exceptionally rich in asparagine residues, many of which are distributed in clusters (2-15 residues) along the polypeptide chain. Unlike many P. falciparum antigens, this protein lacks tandemly repeated sequences. The antigen is distinct from Pf 155, a merozoite-derived antigen deposited in the membrane of infected erythrocytes, but contains epitopes that crossreact with anti-Pf 155 antibodies. Antisera prepared in mice against the asparagine-rich protein react with late-stage parasites in indirect immunofluorescence. In an in vitro merozoite reinvasion assay, the IgG fraction of a mouse polyclonal antiserum, as well as a mouse monoclonal antibody, gave significant inhibition. Three polypeptides (Mr 36,000, 30,000, and 15,000) were recognized by these antibodies on immunoblots of P. falciparum extracts.