During early pregnancy, in response to the implanting embryo, the surrounding uterine stroma undergoes a dramatic transformation into a specialized tissue known as the decidua. The decidua encapsulates the developing embryo, facilitating nutrient transfer and limiting trophoblast invasion. Here we show that female mice with a null mutation of the interleukin-11 receptor alpha chain are infertile because of defective decidualization. A temporal analysis revealed IL-11 expression is maximal in the normal pregnant uterus at the time of decidualization, and in situ hybridization studies showed expression of the IL-11 and the IL-11 receptor alpha chain in the developing decidual cells. These observations reveal a previously unrecognized critical role for IL-11 signaling in female reproduction.