The ability of inbred mice to make a specific immune response to an optimal dose (10 µg) of the random copolymer GLØ is under the control of a distinct autosomal dominant gene. This gene is associated with the major histocompatibility locus of the species. Mice with the H-2 alleles d and q are responders, whereas those with alleles a, b, k, p and s are non-responders. This association with the H-2 locus was determined by use of recombinant-inbred strains and confirmed by the use of inbred and congenic strains. The application of RI strains to help identify Ir gene associations to H-2 is discussed.