Genes homologous to heat shock protein 70 have been described in parasitic protozoa. It has been proposed that they may be important to the parasite as it moves from the vertebrate host at 37 degrees C to the insect. We now describe a genomic DNA clone isolated from Plasmodium falciparum that encodes a protein similar in sequence to a mammalian heat shock-related protein, the 78-kDa glucose-regulated protein of rat and hamster. The gene is expressed during the erythrocytic stage in both asexual and sexual parasites (RNA blot analysis) and a 72-kDa protein is immunoprecipitated from erythrocytic stage parasites. Importantly, the sequence of the clone is similar to the canonical sequence at the carboxyl termini of glucose-regulated proteins of mammals that determines their localization within endoplasmic reticulum. Since the parasite sequence has only three (Asp-Glu-Leu) of the four carboxyl-terminal amino acids, its location and its function within the parasite remain to be determined.