The Plasmodium berghei sporozoite antigen-specific T cell repertoire was analyzed in C57BL/6 (H-2b), BALB/c (H-2d) and C3H/HeN (H-2k) mice following immunization with irradiated sporozoites. Proliferative responses were correlated with the protective status of each strain. Proliferative reactivities to sporozoite antigens were compared in cultures containing either CD4+ T cells, CD8+ T cells, or total splenic lymphocytes. CD8+ T cells had no proliferative activity to sporozoite antigens; CD4+ T cells and splenic lymphocytes responded to the priming antigen, but the responses varied according to the mouse strain tested. The proliferative activity diminished at the onset of protection, presumably due to the induction of regulatory or non-proliferative T cell subsets. Sporozoite-immune lymphocytes did not respond to P. berghei circumsporozoite synthetic peptides. The restricted utilization of T cell epitopes during anti-sporozoite responses can be interpreted as resulting in part from a limited processing of the CS protein antigen.