The finding that HLA-DR compatibility assessed by DNA typing correlates with short-term graft outcome better than serology prompted us to study the degree of genomic HLA-DR compatibility on 55 patients with a graft functioning for more than 10 years (group A), compared with 82 patients with more recent transplants regardless of survival (group B). Because adequate blood donor samples were not available for group A long-term survivors, we used donor renal cells obtained by fine needle aspiration biopsy as a source of DNA. We found that in long-term survivors, the distribution of HLA-DR mismatches was significantly different from that observed in group B patients. In particular, whereas a similar proportion of patients with 1 mismatch was seen in both groups, 27.3% of group A patients vs. 6.1% of group B patients had no mismatch, and 23.6% of group A vs. 41.5% of group B patients received transplants with no HLA-DR compatibility (P = 0.001). We also investigated a possible correlation between number of incompatibilities and graft function. Well-matched patients received less steroid pulses than less well-matched recipients, and steroid-resistant rejection episodes were more common among less well-matched recipients. These results suggest a prognostic role of genomic HLA-DR compatibility on long-term success of cadaver kidney transplantation.