Six families with familial malignant melanoma (FMM) were HLA-A, -B, and -C typed to ascertain whether or not FMM would segregate with the HLA complex. The HLA-B12 antigen was present in five of the six families. In three families the HLA-FMM linkage could be analyzed: linkage was possible in two but not in the third. These findings suggested that two types of FMM may exist: a more frequent type (five cases) that apparently segregates with the HLA complex and another (one case) that does not segregate with the HLA complex. Moreover, a factor included in the HLA region or another factor linked to it may have played an important role, in five of the six families, in FMM pathogenesis, whereas in the sixth family its role may have been performed by some other factor. These findings are consistent with the hypothesis of two complementary factors (one of which was included in the HLA complex) for the promotion of FMM with dominant inheritance and high penetrance.