Previous studies have shown that influenza virus-immune cytotoxic T lymphocytes can recognize virus in conjunction with self HLA-A2 antigens. Nevertheless, the virus-infected target cells from one HLA-A2-positive male donor (designated M7) could not be lysed by the virus-immune cytotoxic lymphocytes from any HLA-A2-matched unrelated donors. Although extensive serological analyses showed no difference between the HLA-A2 antigens of donor M7 and other HLA-A2-positive donors, isoelectric focusing of the HLA-A2 molecule from donor M7 revealed a clear difference in the heavy polypeptide chains when compared with the HLA-A2 molecules of other donors. The present study demonstrates that the HLA-A2-restricted anti-H-Y cytotoxic T lymphocytes obtained from a female aplastic anaemia patient fail to lyse the male M7 target cells, whereas the HLA-A2-restricted anti-H-Y antibodies from the same patient react with the cells of donor M7. These results suggest that: (a) HLA-A2-restricted anti-H-Y antibodies can recognize self determinants on the HLA-A2 molecule that are distinct from those that are recognized by HLA-A2-restricted anti-H-Y cytotoxic T cells; and (b) HLA-restricted T and B cells may use different receptor repertoires for the recognition of foreign antigens such as H-Y.