Background.Matching for the HLA class I loci A and B and for the HLA class II locus DRB is known to influence the survival rate of kidney transplants. It is unknown whether matching for the HLA class II locus DPB also exerts an influence on graft outcome.Methods.The influence of matching for the HLA-DPB locus was analyzed based on DNA typing results obtained in more than 3600 first and 1300 repeat cadaver kidney transplants.Results.HLA-DPB mismatches had no deleterious influence on the outcome of first cadaver transplants. However, the influence was statistically significant for retransplants. One-year graft survival rates were 83±2% with no mismatch (n=345), as compared with 76±2% with one mismatch (n=702,P=0.02), and 73±3% with two mismatches (n=258,P=0.003). The deleterious influence of HLA-DPB mismatches was particularly strong in retransplant recipients with >50% reactivity of preformed lymphocytotoxic antibodies, for which the 1-year graft survival rate was 70±4% with no mismatch, as compared with 69±3% with one mismatch (P=0.05) and 61±5% with two mismatches (P=0.003).Conclusions.These results indicate that HLA-DPB is a clinically relevant histocompatibility locus in cadaver kidney retransplantation. It is proposed that prospective typing and matching for HLA-DPB should be implemented for cadaver kidney retransplants.