Genetic factors may contribute to the development of an aberrant pro-inflammatory immune response during pregnancy, thereby increasing the risk of some pregnancy-related pathologies such as recurrent spontaneous abortion (RSA). Interleukin 1 receptor antagonist is an important anti-inflammatory molecule encoded by the IL1RN gene, in which an intronic polymorphism has been described. Even though the molecular genetic mechanisms are not understood, this non-coding polymorphism, and especially IL1RN*2, has been associated with several chronic inflammatory and autoimmune diseases. IL1RN*2 is also associated with increased activity of IL-1beta, which is an important pro-inflammatory cytokine. We investigated the genetic variants of IL1RN in 37 Finnish women with RSA and 800 randomly selected Finnish blood donors. The women with RSA showed a significantly increased frequency of genotypes bearing the rare allele IL1RN*3 compared to the blood donors (10.8 vs 2.1%, odds ratio 5.6, 95% CI: 1.5-19.0, P=0.006). Our results suggest that IL1RN polymorphisms may predispose to RSA in a small subgroup of patients.