Plasmodium falciparum is a protozoan parasite that causes malaria. It exhibits considerable antigenic heterogeneity which may be a major problem in developing an effective vaccine against malaria. The S-antigen of Plasmodium falciparum is a highly diverse, heat stable protein that is located in the parasitophorous vacuole of the mature asexual intraerythrocytic parasite. The S-antigen gene consists of multiple alleles that originate from the same chromosome site. The amino acid sequence of each allele contains a large central section of tandemly arranged, nearly identical peptides that are specific to each allele. Thus, directed against the repeat region of a particular allele can be used to define the serotype of an S-antigen. Flanking the central repeat block are two short regions of non-repetitive sequence which occur in four different forms, each of which is utilized to define a single S-antigen family. Comparison of the four S-antigen families reveals t hat they differ considerably from each other with variation being most pronounced in the C-terminal-flanking region.