A major mechanism whereby malaria parasites evade the host immune response to give chronic infections in patients' blood for months, or even years, is antigenic variation. In order to generate variant antigens, parasites require large multigene families. Although several gene families involved in these phenomena have been identified in the human malaria Plasmodium falciparum, to date no variant antigen gene families have been identified in malaria species that will infect widely used rodent laboratory hosts. Here we present, for the first time, to our knowledge, a large multigene family conserved in both rodent and human malarias, which is a strong candidate as a major variant antigen gene family. In each of four species of Plasmodium, three rodent malarias and the human pathogen P. vivax, homologues of the gene family were found to have a conserved three-exon structure. In the rodent malaria P. chabaudi, transcription of members of the gene family was developmentally regulated with maximum expression in late trophozoite stages, which is the developmental stage known to express variant antigen proteins.