Immunization with streptococcal group A vaccines revealed significantly higher immune responses in BALB/c than C57BL/6, CBA, and DBA/2 mice. In general, the antibody response of BALB/c mice not only was markedly hgher than that of the other strains, but also showed a high degree of restriction. With two exceptions, all immune sera of the BALB/c mice exhibited bands in very similar electrophoretic positions. On the other hand, the three other strains were low responders which, except for the DBA/2 mice, rarely demonstrated clear-cut bands in the immune sera.Studies with thymusless (nude) mice carrying 50 -85 % BALB/c genome identified the streptococcal group A polysaccharide, presented on whole bacteria, as a thymus-dependent antigen. These nude mice, after reconstitution with thymus cells, produced group A antibodies restricted to two antibody bands extremely similar to those of BALB/c mice. High levels of antibody were produced in mice reconstituted with low responder DBA/2 thymus cells, indicating that the magnitude of the response is entirely controlled by mechanisms at the bone marrow cell level. Magnitude and restriction of the antibody response to this antigen are not determined by the H-2 allele and are not related to the Iga allotypic marker on the heavy chain.