Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring competitive inhibitor of interleukin-1 (IL-1)-induced proinflammatory activity. The IL-1RA gene is polymorphic, resulting in quantitative differences in both IL-1RA and IL-1beta production. Persons homozygous for allele 2 of the IL-1RA gene (IL1RN*2) have a more prolonged and more severe proinflammatory immune response than persons with other IL-1RA genotypes. Thus, being IL1RN*2 homozygous might be beneficial when combating infectious agents or malignantly transformed cells, but it might be detrimental for those with chronic inflammatory conditions or who are pregnant. The IL1RN*2 phenotype is associated with ulcerative colitis and Crohn's disease, lupus erythematosus, vulvar vestibulitis, and possibly with osteoporosis and coronary artery disease. IL1RN*2 homozygosity may also be associated with recurrent spontaneous abortion, preterm birth, and severity of preeclampsia. Conversely, there are negative associations between IL1RN*2 homozygosity and vaginal colonization with mycoplasmas, infection with human cytomegalovirus and Epstein-Barr virus, human immunodeficiency virus proliferation, and the occurrence of ovarian cancer.