The gene responsible for hereditary hemochromatosis (HH) is tightly linked to the class I region of the human leukocyte antigen (HLA) complex. Initial studies designed to map the disease locus have relied on serological markers for the class I antigens. Molecular markers from this region can now be used in combination with HLA serotyping for mapping studies. We previously reported two pedigrees in which serological data indicated recombinant events within the class I region. These data suggested a location for the HH locus between HLA-A and HLA-B. Molecular mapping studies have allowed us to demonstrate that an apparent recombination in one pedigree did not occur. This approach has also produced a more precise centromeric boundary for the region containing the disease locus, telomeric of HLA-C. These results emphasize the importance of including both serological and molecular markers in pedigree studies aimed at fine mapping the HH locus.