Major histocompatibility differences between mother and fetus may facilitate implantation and maintenance of pregnancy. Thus, we have investigated the compatibility of HLAs in couples with three successive failed IVF-ET cycles. The study couples (n = 15) shared a statistically greater number of HLAs than IVF couples achieving a viable pregnancy with their first IVF-ET attempt (n = 15) and a control group of 100 fertile couples. No difference between fertile and infertile control couples was observed regarding HLA sharing. Thus, we conclude that some cases of unsuccessful ETs after IVF might be caused by underlying close histocompatibility between partners.