The gene for hereditary hemochromatosis is linked to the HLA locus on chromosome 6. Four cloned DNA probes originating from the HLA class I region were used to detect seven restriction fragment length polymorphisms (RFLPs). Allele frequencies and segregation of each RFLP was determined. Analysis of RFLPs in 38 unrelated homozygotes with hemochromatosis revealed differences in allele frequencies between the control and the hemochromatotic groups but these differences did not reach statistical significance. Some differences persisted, however, even when only controls with the A3 antigen were compared with A3 hemochromatotics. Since both control and hemochromatotic groups were small, further studies will be necessary to ascertain whether these RFLPs could serve to locate the gene responsible for hereditary hemochromatosis.