In healthy individuals, like in highly sensitized patients, CTL precursors (CTLp) frequencies against HLA-A antigens were found to be significantly lower than CTLp frequencies against HLA-B antigens. In the present study, we tested whether not only quantitative but also qualitative differences exist between CTLs against HLA-A antigens versus HLA-B antigens. Experiments performed in the presence of antibodies against CD8 showed that CTLp directed against HLA-B antigens were significantly less inhibited by anti-CD8 compared with CTLp against HLA-A. The low anti-CD8 inhibition of the CTLp directed against HLA-B antigens may be explained by a higher affinity of the CTLp for HLA-B antigens on the target cells. CTLp directed against HLA-B antigens were also found to be less sensitive to CsA, which suggests that their high affinity is due to previous priming. A clinical relevance of these findings is suggested by the observation that matching for HLA-B antigens is of greater importance for kidney graft survival than matching for HLA-A.