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The impact of HLA-DR antigen matching on the survival of cadaveric renal allografts was assessed in 158 consecutive transplants performed in our unit since early 1978. In 41 donor-recipient pairs with two shared HLA-DR antigens, the actuarial graft survival rate at 6 months was 73 as compared with 51 in 76 transplants with one HLA-DR antigen shared and 32 in 41 transplants with zero shared HLA-DR antigens. This finding is highly significant (Pfor heterogeneity [PH] = 0.0005 and Pfor trend, [PT] = 0.0001). Our data clearly indicate that HLA-DR antigen sharing is more beneficial than merely avoiding HLA-DR incompatibility. But, the frequent antigen HLA-DRw6 was not taken into account in this study due to difficulties in its identification. We found no evidence that the observed beneficial effect of HLA-DR matching could be explained by interaction of other prognostic factors, such as sex, age, previous transplantation, diabetes mellitus or pretransplant blood transfusion. Patients who did not receive blood transfusion prior to transplantation had a significantly lower graft survival rate than those who did (13 vs. 56 at 6 months). HLA-DR matching was found to have a powerful effect on graft survival even among pre-transplant blood transfused recipients (PH= 0.002, PT= 0.0006). We conclude that selection of recipients for transplantation should attempt to achieve HLA-DR identical combinations.