The anamnestic antibody response to synthetic peptide antimalarial vaccines is under Ir gene control. It has therefore been inferred that the development of antibody responses to the native repetitive Ag of malaria parasites also requires linkage of T and B cell epitopes, presentation of Ag in the context of MHC class II components, and cognate T cell help for antibody production. In this study, we sought to test this assumption, by utilizing classical protocols to determine whether the antibody response to the repetitive surface Ag of malaria sporozoites, the circumsporozoite (CS) protein, is under Ir gene control. In contrast to vaccine constructs, such as recombinant proteins or synthetic peptides, secondary responses to the repetitive oligomeric domains of the native CS protein of intact malaria sporozoites do not require the presence of Ag-specific Th cells. Conferral of CS-specific Th cells does not appear to influence the magnitude of this thymus-independent response to sporozoites. In further contrast to synthetic CS analogs, exposure to the parasite appears to be associated with low levels of Ag-specific Th cell sensitization. These observations suggest a functional role in immune evasion for the immunodominant repetitive domains found within protein Ag of malaria and other parasites.