It has remained to be established that matching of the HLA-DP antigen plays a key role in bone marrow transplantation (BMT), mainly due to the difficulty of the primed lymphocyte test (PLT) method for DP typing. We previously reported an efficient technique for HLA class II genotyping, by digestion of polymerase chain reaction (PCR)-amplified genes with restriction fragment length polymorphisms (RFLP) endonucleases (PCR-RFLP method). DNAs from 46 recipients and corresponding donors in serologically HLA-identical sibling-BMT cases were DP typed by this PCR-RFLP method. Of the 46 cases, five (10.9%) were genetically DP mismatched (recombinant frequency between the DR-DQ and DP subregions was at least 2.7% per meiosis), providing an important opportunity to look at the effect of the disparity only seen in the DP antigen on BMT. Three of the four DP-mismatched BMT cases that could be evaluated developed severe acute graft-versus-host disease, suggesting that DP disparity played an important role in BMT.