The causes of failure were studied for 1386 cadaver kidney transplants shared through the UNOS 6-antigen match program from November 1987 to February 1992. The one-year graft survival for 1004 HLA-matched first cadaver transplants was 88% compared with 90% for parent donor and 78% for 22,188 HLA-mismatched first cadaveric donors reported to the UNOS Scientific Renal Transplant Registry. The cause of graft loss was immunological in 55% of HLA-mismatched cadaver kidney failures, whereas only 39% of the HLA-matched graft failures were immunological. The fraction of immunological failures in HLA-matched first transplant recipients younger than age 17 was 57% and decreased with increasing age to 14% for recipients older than age 60. Death with a functioning graft accounted for 50% of failures in the older age group. Sensitization was associated with an increased incidence of immunological failures in matched first graft recipients from 36% in nonsensitized to 53% in broadly sensitized patients, and 55% of failures were immunological in second graft recipients compared with 39% in first transplants. Some immunological failures may have been due to tissue typing, since only 18% of failures in kidneys with well-defined HLA antigens were immunological, whereas 44% of kidneys matched with more difficult HLA antigens were lost due to immunological causes. The results indicate that phenotypically identical cadaver renal transplants have a reduced rate of immunological failures. As the accuracy of this tissue typing for the more difficult HLA antigens improves, immunological failures in this group of transplants will decline even further.