The involvement of the Class I HLA-A2 antigen is briefly reviewed in relation to allograft rejection, the fete-maternal relationship, viral cytotoxic reactions and tumor immunity. It is suggested that the HLA-A2 molecule may have, as compared to other HLA Class I alleles, a dominant role as a restricting element in cytotoxic T-cell recognition in the fete-maternal relationship to male fetuses, in specific viral infections and in tumors. As compared to other HLA Class I alleles, its reduced expression or loss in a variety of tumors suggests its possible important role in tumor immune surveillance. The disappearance of HLA-A2 from tumor cells may eventually contribute to the escape from T-cell recognition of malignant cells.