To test the hypothesis that noninherited maternal antigens (NIMA) can modulate the alloreactivity of infant cells and provide protection for renal transplant recipients, a study of renal transplantations performed between 1980 and 1991 was undertaken. The survival rate of grafts with a mismatched antigen identical to the NIMA was compared to that of grafts in which the mismatched antigen was not identical to the NIMA. In the case of HLA-A mismatches, graft survival rates were significantly better for NIMA-mismatched transplants: 94% and 83% at 1 and 3 years, respectively, for single NIMA HLA-A mismatched transplants, and 83% and 67% when both HLA-A antigens were mismatched, compared to 76% and 68% (one non NIMA HLA-A mismatch) and 67% and 45% (two non-NIMA HLA-A mismatches). Our results suggest that some class I NIMA-mismatched antigens are not harmful to renal transplant recipients.