The antibody response to the 2,4,6-trinitrophenyl hapten (TNP) conjugated to autogenous mouse serum albumin (MSA) is regulated by an Ir gene(s) located within the major histocompatibility complex (MHC). Both the qualitative and quantitative ability of congenic strains to produce TNP-specific antibodies are functions of the H-2 haplotype. Thus, mouse strains may be classified as high (H-2d), intermediate (H-2b&s), and low responders (H-2a,k,n,p&q). Antibody responses measured by antigen-binding capacities in modified Farr assays were compared among many strains carrying recombinant H-2 haplotypes and their hybrid progenies. The gene locus controlling specific responsiveness to TNP-MSA, now designated Ir-6, was mapped within the I-B subregion of the H-2 complex. Recessive inheritance of high responsiveness was confirmed in hybrid progenies of three different low × high responder crosses. IgG1 and IgM TNP-antibody levels of high and low responder mice were separately determined by solid phase radioimmunoassay using class-specific antisera.