At the human maternal-fetal interface, the decidua forms a dense matrix that is believed to limit trophoblast invasion. We investigated whether the metastasis suppressor KAI1 (CD82) is expressed at the maternal-fetal interface. Immunohistochemistry showed strong expression of KAI1 in decidual cells, whereas trophoblast cells were negative for KAI1. In luteal phase endometrium, KAI1 was present in decidualizing endometrial stromal cells. We investigated whether KAI1 expression in endometrial stromal cells is regulated by the decidualizing stimuli cAMP and progesterone or by the cytokine interleukin (IL)-1beta. Western blot analysis revealed induction of KAI1 protein by cAMP analog, but not by progesterone, in a delayed fashion. In contrast, IL-1beta rapidly stimulated KAI1 expression at the transcript level and at the protein level. Cultured decidual cells from term placenta expressed a basal level of KAI1 protein that was elevated on cAMP stimulation. Silencing of KAI1 by RNA interference attenuated expression of decorin, a decidual product implicated in limiting trophoblast invasion. This study shows for the first time the expression of KAI1 in decidual cells at the human maternal-fetal interface, where the metastasis suppressor might participate in intercellular communication with trophoblast cells and the control of trophoblast invasion.