Abstract: HLA-G is a nonclassical, class I major histocompatibility complex (MHC) gene that exhibits immunomodulatory properties and likely plays a role in the maintenance of successful pregnancy. In this study, we investigated the role of HLA-G polymorphisms on risk for recurrent pregnancy loss (RPL) and on circulating levels of soluble (s)HLA-G in Iraqi women. DNA and plasma were obtained from blood samples collected at 9–12weeks gestation from 50 women with RPL and 50 healthy pregnant women in Basrah province, Iraq. As measured by ELISA, median sHLA-G levels were significantly lower in the RPL cases compared to healthy controls (21.4 vs. 38.8U/ml, respectively; P =0.025), and decreased with increasing maternal age (P =0.0051). However, HLA-G allele and haplotype frequencies did not differ significantly between cases and controls (P values ⩾0.12 for all tests). In contrast, homozygosity for the C allele (CC) at a tri-allelic promoter polymorphism, −725C/G/T, was associated with lower concentrations of sHLA-G compared to the CG or CT genotypes (median levels 21.1 vs. 40.1 vs. 42.6U/ml, respectively; P =0.0089). These results demonstrate that HLA-G genotype influences circulating sHLA-G levels during pregnancy but is not significantly associated with risk of RPL. [Copyright &y& Elsevier]