There is impressive evidence from geographical data, studies in the field and in vitro culture work that genetically determined deficiency of glucose 6-phosphate dehydrogenase (G6PD) confers relative protection against the human malaria parasite, Plasmodium falciparum. G6PD is encoded by an X-chromosome-linked gene, and protection phenomenon is manifested in heterozygous females who are genetic mosaics but, surprisingly, not in hemizygous males with complete deficiency. We have shown previously that the parasite, when passaged serially through G6PD-deficient red cells, undergoes adaptive changes that gradually improve its ability to multiply in these deficient cells. To explain the above paradox, we now show that this adaptive process is associated with, and may consist in, the induction of synthesis of a novel G6PD coded by Plasmodium falciparum.