Background.In this large, two-center study, 260 cytotoxic T lymphocyte precursor (CTLp) frequency assays, performed to assess patient-donor compatibility, were analyzed in relation to the degree of HLA matching.Methods.While the tissue-typing techniques used at the Royal Postgraduate Medical School (RPMS) and Anthony Nolan Bone Marrow Trust (ANBMT) differ, the results of the analyses on the two sites are analogous, with high CTLp frequencies (> 1:100,000) in 42% and 41% of recipient-donor pairs, respectively.Results.Recipient-donor combinations with class I mismatches and class II identity were associated with high CTLp frequencies (collectively 83% vs. 17% low CTLp). This correlation was not as strong in pairs where class II mismatches were demonstrated (61% high vs. 39% low). Despite using different matching procedures, the RPMS and ANBMT both show that 32% of the“perfectly” matched pairs (i.e., where no mismatch was detected by any of the techniques used here) had high frequencies of recipient-specific CTLp.Conclusions.The failure of conventional methods to identify such a level of histoincompatibilities indicates that the CTLp assay has an important role in the selection of unrelated donors for bone marrow transplantation.