The question of whether or not HLA is important in transplantation can now be answered with a definite yes. The nationwide six-antigen-matching program, in which over 100 US transplantation centers have participated, has shown that a high (88% to 90%) 1-year graft survival rate can be achieved when kidneys are shipped to well-matched recipients. Long-term outcome (measured as half-life) is also markedly improved, from an average of 7 years for cadaveric donor transplants to as much as 19 years in the six-antigen-matched recipients. One of the major factors influencing long-term survival is histocompatibility matching, as shown by the survival differences among HLA-identical siblings (25-year half-life), one-haplotype-mismatched parental donors (12-year half-life), and two-haplotype-mismatched cadaveric donors (7-year half-life). For the past 25 years of kidney transplant experience, cadaveric donor half-life has remained stable at 7 years, despite many improvements in immunosuppression protocols. Histocompatibility matching unquestionably offers the best approach to prevention of chronic rejection.