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<p>Abstract</p> <p>Background</p> <p>The variant surface antigen family <it>Plasmodium falciparum </it> erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors. The sequence diversity and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence.</p> <p>Methods</p> <p>Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 <it>var </it>and <it>rif </it>genes as well as <it>var </it>genes of other parasite strains.</p> <p>Results</p> <p><it>var </it>genes can be sub-grouped into three major groups (group A, B and C) and two intermediate groups B/A and B/C representing transitions between the three major groups. The best defined <it>var </it>group, group A, comprises telomeric genes transcribed towards the telomere encoding PfEMP1s with complex domain structures different from the 4-domain type dominant of groups B and C. Two sequences belonging to the <it>var1 </it>and <it>var2 </it>subfamilies formed independent groups. A <it>rif </it>subgroup transcribed towards the centromere was found neighbouring <it>var </it>genes of group A such that the <it>rif </it>and <it>var </it>5' regions merged. This organization appeared to be unique for the group A <it>var </it>genes</p> <p>Conclusion</p> <p>The grouping of <it>var </it>genes implies that <it>var </it>gene recombination preferentially occurs within <it>var </it>gene groups and it is speculated that the groups reflect a functional diversification evolved to cope with the varying conditions of transmission and host immune response met by the parasite.</p>