The shortage of cadaver kidneys relative to increasing demand for transplantation has lead to a remarkable rise in transplantation from living donors. Based upon data reported to UNOS, the number of living donor kidneys transplanted in 2000 (5,106) nearly equaled the number of cadaver kidneys from preferred donors aged 6-50. HLA-mismatched siblings, offspring, spouses and other genetically unrelated donors accounted for nearly 80% of increased living donor transplantation during 1994-2000. Despite the increased use of poorly HLA-matched living donor kidneys, the actuarial 10-year graft survival rates for transplants between 1988-2000 were clustered between 53-57% for HLA-mismatched living donor grafts, except for offspring-to-parent transplants (49%) when the recipients were generally older. The 10-year survival rate for 96,053 cadaver grafts was 38% during the same period. The 5-year graft survival rates for more recent (1996-2000) cadaver donor transplants were 66%, 62% and 56% for recipients of first, second and multiple grafts, respectively (p < 0.001). The comparable results among recipients of living donor kidneys were 67%, 66% and 59% (p = ns). The 5-year graft survival rates for HLA-matched first grafts were 7% higher than those for HLA-mismatched transplants when the kidney was from a living or cadaver donor. HLA-identical sibling transplants provided the best long-term graft survival (85% at 5 years and a 32 year half-life). Even with improved crossmatch tests and stronger immunosuppression, sensitization was associated with 8% lower graft survival at 5 years and with a higher rate of late graft loss among first cadaver kidney recipients. Sensitization also was associated with an increase in delayed graft function from 22% of unsensitized first transplant recipients to as much as 36% among multiply retransplanted patients. Recipient race was a key factor in long-term graft survival of both living and cadaver donor kidneys. The rate of late graft loss was double among blacks compared with recipients with other racial origins whether the kidney was from a living or cadaver donor. Black recipients accounted for 29% of first cadaver transplants during 1996-2000, but only 14% of living donor grafts. Thus an important component of long-term differences in graft survival comparing living and cadaver donor transplants is the disparate racial demographics. Both the recipient and donor populations are aging. The proportion of cadaver kidney recipients over age 50 increased from 26% to 45% and the proportion of living donor kidney recipients over age 50 rose from 10% to 35% between 1988 and 2000. The aging population affects the transplant outcome as 65% of graft losses among young recipients (ages 10-15) were attributed to acute or chronic rejection compared with only 25% of grafts lost among patients over age 60. More than half of graft losses among older recipients were due to death with a functioning graft. Kidneys from donors over age 60 comprised 9% of first cadaver transplants and yielded a 50% 5-year graft survival rate compared with 70% when the donor was aged 19-45. Kidneys from donors over age 60 accounted for only 3% of first living donor transplants and their 84% 5-year graft survival rate was comparable to that for younger donor kidneys. Despite declining immunological graft losses with advancing recipient age, the effect of HLA matching was similar among recipients of first cadaver transplants aged 50 or under and those over age 50. Completely HLA-mismatched grafts had a 10% lower 5-year graft survival rate than HLA-matched grafts when the recipient was over 50 compared with a 14% lower survival rate in younger recipients. The graft half-lives were shorter by 5-7 years for HLA-mismatched kidneys transplanted to older or younger recipients, respectively.