The distribution of MHC antigens in human melanocytic lesions, i.e. HLA class I and HLA class II antigens is reviewed. HLA class I antigens have a broad distribution, but may be lost during tumor progression. In contrast, HLA class II antigen expression appears with neoplastic transformation. The mode of regulation of HLA antigens in melanoma lesions is complex. Immunohistochemical demonstration of HLA antigen expression in primary melanoma lesions and in locoregional metastases has prognostic relevance. Expression of HLA-DR in primary melanoma lesions is associated with an unfavorable prognosis, as is a decreased expression of HLA-A,B,C antigens in locoregional metastases.