Previously we have reported the precise determination of the entire antigenic structure of sperm-whale myoglobin. This protein which is made up on a single polypeptide chain (153 residues, m.w. 17,816) has five antigenic sites located in exposed conformationally sensitive continuous portions of its polypeptide chain. The five antigenic sites occupy the following regions: Site 1: sequence 15–22; Site 2: sequence 56–62; Site 3: sequence 94–99; Site 4: sequence 113–119; Site 5: sequence 145–151. We investigated the genetic control of T lymphocyte proliferative response to myoglobin and its synthetic antigenic sites in mice (PETLES Assay). Two parts of the myoglobin molecule (sequences 1–6 and 121–127) that were not within antigenic sites were also synthesized and employed as controls. Also used as control was a synthetic ‘nonsense’ heptapeptide that did not resemble any part of myoglobin. Haplotypes H-2d, H-2f and H-2s gave substantial T lymphocyte proliferative response to whole myoglobin whereas haplotypes H-2d, H-2k, H-2p, H-2q and H-2r were low responders.