Two Ir genes in distinct I-subregions of H-2 have been shown to control the antibody response to sperm whale myoglobin (Mb) in mice (Berzofsky, J. A., J. Immunol. 120, 360, 1978). B10.D2 (H-2d) mice (high responders) have both Ir-Mb-1 (in I-A) and Ir-Mb-2 (probably in I-C), while B10 (H-2b) and B10.BR (H-2k) mice (low responders) have neither. Recombinant strains B10.A and B10.A(5R) with only Ir-Mb-2 are intermediate in response to whole Mb. However, when the same sera were tested for antibodies binding to fragment (132–153), B10.A 3° sera, which had 6-fold more anti-Mb than B10.BR sera, had no more antibody to this fragment (whereas the B10.D2 sera had 10-fold more anti-(132-153)). Similarly, the B10.A(5R) sera had barely more anti-(132-153) than B10 sera, even though they had 4-fold more total anti-Mb. Conversely, D2.GD mice (with only Ir-Mb-1) made as much anti-(132–153) in the anti-Mb sera as did congenic DBA/2 mice, with both genes.