Human leukocyte antigen G (HLA-G) is a non-classical Ib molecule in the major histocompatibility complex. HLA-G has important immunosuppressive properties, and in the context of cardiac transplantation, is associated with a low risk of cellular rejection. A 14-bp insertion/deletion polymorphism in exon 8 of the HLA-G gene is associated with messenger RNA (mRNA) stability and expression of HLA-G. This study analyzed the relationship between HLA-G polymorphisms and serum HLA-G levels in patients after cardiac transplantation to determine if any specific HLA-G genotype is associated with cellular rejection.Ninety-four heart transplant patients were genotyped for the 14-bp polymorphism. Serum HLA-G levels and cellular rejection grades were evaluated in all patients.The 14-bp polymorphism was significantly associated with serum HLA-G expression. Patients with the -14-bp/-14-bp genotype had significantly higher mean serum HLA-G levels (88.2 U/ml) than those patients with the +14-bp/-14-bp (52.8 U/ml) and +14-bp/+14-bp (32.2 U/ml) genotypes (p = 0.004). The -14 bp/-14-bp genotype was significantly associated with fewer episodes of cellular rejection.This study suggests that the 14-bp deletion in the HLA-G gene plays an important role in the expression of HLA-G and thus might be a clinically useful genetic indicator for cellular rejection risk after cardiac transplantation.