Numerous polymorphic antigens of the asexual erythrocytic stages of P. falciparum are now well characterized. Diversity in some of these antigens, including MSA-1, MSA-2 and the S-antigen is associated with changes in the repeat sequences which are frequently a prominent structural feature of malaria antigens. It is not known whether the variation in repeats causes allelic gene products to adopt different conformations but variation in and around the repeats in SPAM, a newly characterized secreted antigen, preserve the unusual alanine-heptad repeats which we assume generate a helical bundle in this protein. Mutations in non-repetitive regions of the S-antigen and in AMA-1, an antigen lacking repeats, are strongly biased towards those which alter the amino acid sequence. This and other evidence indicates the operation of biological selection but the role of immune responses as a selection pressure operating on these diverse antigens remains to be established.