A cDNA clone expressing a Plasmodium falciparum blood-stage antigen in Escherichia coli was identified by colony immunoassay using immune human sera. Antibodies affinity-purified on extracts of this clone reacted with both asexual blood stages and sporozoites of P. falciparum, recognizing a Mr23,000 protein in the blood stages. The nucleotide sequence of the cDNA revealed a signal peptide and an internal hydrophobic sequence typical of transmembrane anchor sequences. Located 3' to the putative anchor are two tetramers, Asn-Ala-Asn-Pro and Asn-Ala-Asp-Pro, which are closely related to the repeats of the circumsporozoite protein of P. falciparum. The blood stage protein is conserved amongst several isolates of P. falciparum, and antibodies against it are common in the sera of individuals living in the area where the parasite is endemic.