The separate influence of HLA-A, HLA-B, and HLA-DR mismatches on short- and long-term kidney graft survival was analyzed in a series of over 40,000 recipients of first cadaver kidney transplants. As expected, during the early posttransplant period, HLA-DR mismatches had a stronger influence on graft survival than HLA-B mismatches, and HLA-A mismatches had a very small influence. Surprisingly, during the period from 6 months to 5 years post transplantation, all three HLA loci had approximately the same influence. When the graft survival computation was started at 100 % at 6 months, the difference between grafts with zero or two mismatches at the end of 5 years was 6 %, regardless of whether HLA-A, HLA-B, or HLA-DR antigens were analyzed. The influence of the three loci was additive so that the survival rate difference between transplants with zero or six mismatches for HLA-A, -B,-DR was 17 % at 5 years. We concluded that, although the HLA-A locus exerts only a weak influence during the early posttransplant course, its influence on long-term survival is comparable to that of HLA-B and HLA-DR. In order to obtain optimal long-term survival, all three loci must be considered in the donor-recipient matching procedure.