DNAs from human melanoma cells, used at early in vitro passage, were evaluated by Southern blot analysis for somatic loss of heterozygosity at the DQ alpha gene. A total of 7 melanomas, 3 primary and 4 metastatic derived from 5 different patients were studied; in one case (pt 665) cell lines were derived from two anatomically different subcutaneous metastasis, whereas in a second case (pt 9923) both the primary tumor and a lymph node metastasis were available. Restriction length polymorphism (RFLP) analysis, performed on autologous peripheral blood lymphocyte (PBL) DNA digested with different enzymes, showed a pattern of bands compatible with the constitutional heterozygous typing at DQ alpha gene in 4 cases whereas 1 case revealed an homozygous typing. When melanoma DNAs were analysed, 1 out of the 4 informative cases (pt 1007) showed a loss of a diagnostic fragment for DQ alpha gene when digested with both Taq I and Bgl I enzymes. These results indicate that class II allelic losses detectable by RFLP can be found on malignant melanoma and add further complexity on the involvement of chromosome 6 whose cytogenetic abnormality are the most consistent in this human neoplasia.