MHC antigen expression on 20 nevi, and 35 primary and 95 metastatic melanomas was studied by immunoperoxidase techniques using monoclonal antibodies to identify the antigens on frozen tissue sections. DR antigens were not detected on nevi but were detected on 71% of primary melanomas and 56% of metastases, suggesting that this antigen may be a useful marker of malignant transformation of nevi. Expression of class II antigen could not be related to other prognostic histological features of primary melanoma such as tumour thickness, but comparison of the common phenotypes of primary and metastatic melanoma suggested that expression of DR antigens alone in the absence of DP, DQ and ABC antigens may be an indicator of metastatic potential. Class I (HLA-A,B,C) antigens were also expressed infrequently on nevi but were detected on 43% of primary melanomas and 34% of metastases. HLA-A,B,C expression was inversely related to thickness of the primary melanoma. This as well as the lower expression of class I antigens on metastases, may indicate that growth and spread of melanoma may be inhibited by MHC (class I) dependent cytotoxic T cell responses. Expression of class I MHC antigens was unrelated to class II antigens. Expression of DR was more common than DP or DQ, but the latter with one exception, were not expressed in the absence of DR antigens. Significant differences were not found in MHC antigen expression on metastases in lymph nodes compared to those in subcutaneous sites, but further studies are needed to determine whether such differences may exist between metastases in other visceral sites.