Gene targeting, the technology that permits inactivation or modification of a gene by homologous recombination, has been reproducibly established in two plasmodial species: Plasmodium falciparum (1) , the most important pathogen for humans, and Plasmodium berghei (2) , which infects rodents. In both species, the red blood cell (RBC) stages of the parasite are transformed and targeting constructs integrate into the genome exclusively via homologous recombination.