Distribution of cadaveric donor kidneys, based upon the donor-recipient HLA match grade, remains one of the major controversies in transplantation. To determine whether matching results in fewer rejection episodes and better graft survival, we retrospectively studied our single-center patient population of 683 cyclosporine-prednisone-treated primary cadaveric renal allograft recipients. For 237 recipients of well-matched HLA A, B kidneys (< or = 2 HLA A, B mismatches [MM]) the 1-, 3-, 5-, and 7-year graft survivals of 76%, 66%, 62%, and 61%, respectively, were not significantly different from those of 71%, 65%, 63%, and 63%, respectively, for the 446 poorly matched HLA A, B (> 2 HLA A, B MM) recipients. Similarly, the 1-, 3-, 5-, and 7-year graft survivals for the 307 recipients of well-matched HLA-DR kidneys (0 or 1 DR MM) of 74%, 65%, 63%, and 61%, respectively, were not significantly different from those of 72%, 65%, 63%, and 62%, respectively, for the 366 poorly matched (2 DR MM) recipients. Patient survivals were comparable at each time point for well- vs. poorly matched recipients. Similarly, donor-recipient HLA A, B, and DR matching was not beneficial in retransplant recipients who were transplanted following negative NIH and antiglobulin (AHG) crossmatches when testing both historical (high-PRA) and pretransplant sera. Since rejection episodes may be a more sensitive indicator of immune response than graft loss, we also analyzed the relationship between donor-recipient HLA match grade and posttransplant rejections. A total of 60% (n = 413) of recipients experienced no rejections and had 1-, 3-, 5-, and 7-year graft survivals of 82%, 78%, 74%, and 73%, respectively; 32% (n = 215) of patients who experienced 1 rejection had 1-, 3-, 5-, and 7-year graft survivals of 58%, 48%, 44%, and 43%, respectively (P < 0.001 for graft survival of 0 vs. 1 rejection). The remaining 8% (n = 55) of recipients experienced more than 1 (> 1) rejection and had 1-, 3-, 5-, and 7-year graft survivals of 62%, 38%, 36%, and 36%, respectively (P < 0.001 for graft survival of 0 vs. > 1 rejection and P < 0.01 for graft survival of 1 vs. > 1 rejection). The mean numbers of rejections/patient experienced by well-matched vs. poorly matched recipients were comparable and not significantly different.(ABSTRACT TRUNCATED AT 400 WORDS)