The genetic control of the low response of BSVS mice to streptococcal Group A carbohydrate (GAC) was studied in crosses with responder A/J mice. F1 mice were responders. In the backcross (BSVS × A/J)F1 × BSVS mice, there were equal numbers of anti-GAC responder and nonresponder mice, indicating genetic control by a small number of major loci. The anti-GAC responses of the backcross mice showed no obligate linkage between responder status and A/J H-2 or IgCH alleles. However, it was observed that the average anti-GAC titers were higher in backcross mice heterozygous at these loci. The above data, a lack of low-responder F2 animals, and the segregation of a non-H-2-, non-IgCH-linked locus in the first and second backcross mice, indicate that the defect in the BSVS anti-GAC responsiveness involves three loci: one linked to H-2, another linked to IgCH, and a third locus -tentatively named Ir-GAC- not linked to H-2, IgCH, or Hbb. © 1977 Springer-Verlag New York Inc.