Previous retrospective studies have demonstrated improved outcome in patients whose donors were marched for non-HLA markers in the MHC as well as for HLA genes. Forty patients receiving transplants from unrelated donors were typed prospectively for HLA and non-HLA markers. Non-HLA markers near HLA-B (beta-block markers) and in the DRB1 introns (delta-block markers) were used to assess MHC match between donors and recipient. Patients whose donors were matched at the beta- and delta-blocks had improved event free survival(63%) compared to patients whose donors were mismatched at one or both blocks (25%) (P <0.05). Patients whose donors were marched at the beta-block had significantly less severe acute graft versus host disease (p <0.05). In order to investigate the basis for improved outcome block matching was correlated with HLA matching as determined by DNA sequencing. Beta-block matching was highly correlated with matching for exons 2 and 3 of HLA-B but less so for HLA-C. Delta-block matching was highly correlated with matching for exon 2 of HLA DRB1. It is concluded that matching for non-HLA markers in the MHC improves matching for HLA genes. Further studies are required to determine whether matching for non-HLA markers improves outcome to a greater extent than matching for the HLA genes alone. Human Immunology 61, 83-91 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.