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Background: Successful trophoblast invasion and transformation of the maternal spiral arteries requires that the pregnant endometrium (i.e., decidua) act in an immunologically paradoxical fashion, accepting the semi-allogenic placenta, while maintaining host defenses against an array of microbial pathogens. In contrast to the growing evidence that the immune surveillance molecules known as Toll-like receptors (TLRs) are expressed by trophoblasts and fetal membranes, to date, no studies have been conducted on the decidua., Methods: Decidual tissues and cells were obtained from women undergoing first trimester elective terminations or repeat Cesarean sections and analyzed at both the protein and mRNA level., Results: We now demonstrate for the first time that human decidua differentially express TLRs and their downstream signaling molecules as well as TLR stimulated induction of cytokine production in the first and third trimester of pregnancy., Conclusions: These findings suggest that the decidua is a critical component of the innate immune response in pregnancy. Moreover, the results have implications for the success or failure of compromised pregnancies in early or late gestation.