Third renal transplants were performed in 31 patients (25 men and 3 women: mean age 33 +/- 11 years) with terminal renal failure. Surgical complications occurred in four of them. Acute rejection crises were frequent (48%). In three cases acute humoral vascular rejection led to loss of the grafted kidney. One patient died within 3 months. The proportion of functioning transplants was 83% at 3 months, 59% at 1 year and 20% at 5 years. Such factors as the concentration of panel-reactive antibodies, a history of previous acute humoral rejection crises or the timing of the previous transplant loss had no influence on the prognosis of the new graft. After a mean observation period of 35, 4 months patients whose HLA-DR antigens matched those of the donor at one or two loci had a markedly higher proportion of functioning renal transplants (69% and 64%, resp.) than patients without HLA-DR compatibility (0%; P less than 0.01). These results indicate that a third renal transplant does not carry any increased perioperative risk, and that the proportion of functioning transplants is good in the short term, though the long-term results are poor. Prolonged survival of the renal transplant can be expected only if there is an optimal HLA-DR match between donor and recipient.