The genetics of the immune response in the mouse were studied by using the antigenically simple, stable, naturally occurring protein ferredoxin (Fd) from Clostridium pasteurianum. The immune status of mice primed and boosted with Fd was assessed by using two parameters of immunity: T cell proliferation and serum antibody production with the ELISA method. In both assay systems, the response has been shown to be H-2 linked: k, b, and s haplotypes respond to Fd, and H-2d mice are nonresponders. It is apparent that different immunoregulatory events modulate the response in the responder strains; these factors become evident in the recombinant analysis of the response and to date an immunoregulatory gene(s) has been mapped to at least the K/I-A subregions. F1 analysis demonstrated a gene dose-dependent response of the strains studied.