Levels of IL-18 were significantly lower in women with recurrent miscarriage (RM) than those without idiopathic RM. IL-18 promoter single nucleotide polymorphisms were previously identified to have an impact on IL18 gene transcription activity and influence the level of IL-18 protein production. The aim of this study was to evaluate whether IL-18 gene polymorphisms are risk factors for idiopathic RM in Chinese Han population. Study subjects comprised of 484 idiopathic RM patients and 468 controls. Three polymorphisms (rs360717, rs187238, rs1946518) in IL-18 gene and serum IL-18 concentrations were assessed. rs187238 variant exhibits significant association with RM in additive and recessive genetic model (additive model p = 1.05 x 10(-4), dominant model p = 0.025, recessive model p = 2.43 x 10(-5)). In contrast, rs360717 and rs1946518 are not significantly associated with RM. Serum IL-18 levels are significantly lower in RM cases than in control (111.98 +/- 93.13 versus 148.74 +/- 130.51 pg/mL, p = 7.42 x 10(-7)). There are lower levels of serum IL-18 in rs187238 homozygous mutant (CC) than homozygous wild-type (GG) in this study population, including cases and control groups (98.31 +/- 86.46 versus 131.87 +/- 115.02 pg/mL, p = 0.015). These results suggest that reduced IL-18 levels and rs187238 variant may contribute to pathogenesis of idiopathic RM in Chinese Han population.