Even when HLA is completely matched in sibling donor transplants, as many as one third of the transplants are lost in 10 years. This means that a second or third histocompatibility locus plays some role in rejection of kidney grafts. We postulate that the second locus is Lewis. First, because among 18 second cadaver donor transplant patients having Lewis antibodies, the 1-year graft survival rate was 32% compared to 61% in 37 patients without Lewis antibodies (P = .02). The Lewis antibodies presumably were produced in the course of rejection of the first graft and had an effect on the success of the second graft. As indirect evidence, Lewis mismatching would be expected to occur more frequently in black patients than white, and correspondingly, a lower graft survival rate was noted in black patients receiving sibling, parent, and cadaver donor grafts.