Forty patients with end-stage chronic renal failure received living donor renal grafts, matched at more than 1 HLA haplotype, over the last 25 years. Of these grafts, 33 were first and 7 were second grafts. All recipients received prophylactic corticosteroids. Thirty-four also received prophylactic azathioprine, and 6, prophylactic cyclosporine. Acute rejection occurred in 65% (11/17) of non-cyclosporine treated grafts when the recipient was given 5 or fewer units of blood preoperatively, but in only 18% (3/17) when more than 5 units were given. High-dose steroid therapy reversed the acute rejection each time. Chronic rejection occurred in 2 grafts. Irreversible rejection did not occur in any second graft. Chronic glomerulonephritis, possibly due to recurrent disease, occurred in 1 graft. Five grafts have been lost, 1 each from technical and immunosuppressive complications, and 3 from incidental death. The 1-year actuarial graft survival rate is 95% and the 10-year rate 84%. All surviving patients lead normal lives without significant health restriction, and employ minimal medication. It is postulated that: 1) acute cellular rejection is HLA-independent, and chronic rejection is HLA-dependent, and 2) hyperacute and chronic rejection are related and are parts of a spectrum of humoral immunity.