We analyzed the effect of matching for HLA class II alleles on corneal graft outcome in a single-center, retrospective study from January 1991 through April 1996. The study involved 81 transplant recipients at high and low risk of corneal graft rejection, who were typed by the polymerase chain reaction-restriction fragment length polymorphism method and who completed at least 1-year of follow-up. The DRB1, DQB1, and DPB1 alleles were analyzed together and transplant recipients were subdivided into groups with matching (one to four alleles matched in the high risk or one to five alleles matched in the low risk) and without matching (no allele matched) for HLA class II. A significantly higher rate of 1-year rejection-free graft survival was revealed in high-risk transplant recipients with matching, compared with those without matching (P=0.0238). We have shown that matching for at least one HLA class II allele was actually beneficial in high-risk transplants. An analysis of matching for each allele separately, detected that only HLA-DPB1 matching was significantly associated with a higher rate of 1-year rejection-free graft survival in high-risk transplant recipients with matching (one or two alleles matched) compared with those without matching (no allele matched) (P=0.0139). In particular, matching for one DPB1 allele was significantly beneficial compared with no matching (P=0.0140). There was no significant effect of HLA-DRB1 and -DQB1 matching (P=0.3177 andP=0.2878, respectively). Furthermore, a strong association between DPB1 matching and 1-year rejection-free graft survival was observed in DRB1-incompatible high-risk transplant recipients (P=0.0308). Nevertheless, no significant effect of DPB1 matching was detected in DQB1-incompatible transplant recipients. Our findings indicate that HLA class II DNA typing is clinically relevant for corneal transplant recipients and that especially HLA-DPB1 matching has a beneficial effect in high-risk corneal transplantation.