Recently discovered Toll-like receptors (TLRs) are essential for the induction of innate immune responses. One member of the TLR family, TLR4 mediates lipopolysaccharide (bacterial endotoxin)-induced inflammatory responses. Although the innate immune system appears to be important in the pathogenesis of infection-induced preterm delivery, the distribution of TLRs in human placenta is poorly understood. Here we investigated the expression of TLR4 protein in 43 human placentas obtained from normal and complicated pregnancies delivered in the second and third trimesters, using immunohistochemistry. TLR4 was localized to the extravillous trophoblasts, intermediate trophoblasts/X cells in the degenerative villi, and villous Hofbauer cells of all preterm and term placentas examined and to the inflammatory cells in placentas with chorioamnionitis (CAM). The villous Hofbauer cells of preterm CAM placentas demonstrated increased TLR4 immunoreactivity compared with those of preterm placentas without CAM or those of term placentas with or without CAM. These results suggest an important role of the villous Hofbauer cells in the activation of innate immune system in response to infectious pathogens in preterm placentas. Elucidation of biological functions of placental TLR4 under physiological conditions requires further investigation.