Three levels of humoral responsiveness (none, high or marginal) were noted following secondary immunization with random linear terpolymer of L-glutamic acid, L-lysine and L-leucine (GLleu). These immune responses were under dual H-2-linked Ir gene control. Gene complementation was observed in appropriate F1 offspring between two nonresponder strains and in selected intra-I region recombinants derived from crossing over between nonresponder parental haplotypes. One of the Ir-GLleu genes, beta, was localized within the I-A or I-B subregions. The other Ir-GLleu locus, termed alpha, was mapped in the I-C or S subregions. Differences in the strain distribution of immune responsiveness to GLleu and related terpolymer GLphe (which is also under complementing Ir gene control) are primarily attributable to differences among the Ir-GLleu and Ir-GLphe beta alleles. A correlation exists between the presence of the Ir-GLleu alpha(¿allele and the gene coding for specificity Ia.7.