Graft failure rates for renal transplantations performed between 1989 and 1994 and recorded in the US Renal Data System database were retrospectively evaluated for interactions between cytomegalovirus and HLA-A, B, and DR loci. Twelve significant interactions were observed. There were significantly greater risks of graft failure for the total effect of cytomegalovirus and donor or matched HLA-DR9, recipient or matched HLA-B-51, and matched HLA-B13. We conclude that further study of renal transplants with these combinations of cytomegalovirus and HLA loci is needed to determine whether the observed interactions should be taken into consideration when matching donors with recipients.