The structure of the parasite-encoded G6PD (PfG6PD) may provide clues about the relative protection against malaria in humans with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We have cloned Pfg6pd cDNA encoding a predicted 856 amino acid residues polypeptide with a calculated molecular mass of > 94 kDa. The predicted amino acid sequence is highly homologous to G6PD from other organisms. Pfg6pd maps as a single or low copy number gene to chromosome 14. The unusually large N-terminus and the distance between the NADP-binding site and G6PD-binding site is novel for the parasite G6PD. The differences between parasite and human G6PD proteins could potentially be exploited for designing new chemotherapeutic agents.