Decidualization of the endometrial stromal cells (ESC), considered to be stimulated by progesterone and/or cAMP, is crucial for embryo implantation and placentation. In this study, we isolated a novel clone encoding decidual protein induced by progesterone (Depp) from a human ESC cDNA library enriched with progesterone-inducible genes. Depp mRNA was expressed in various human tissues including placenta, ovary and kidney. Increased expression of Depp was observed in endometria during mid- and late-secretory phases and 1st trimester deciduas. In vitro, Depp mRNA was induced in ESC within 30 min of progesterone treatment, which was inhibited by the antiprogestin RU486. Androgen alone also induced Depp expression. Depp increased the level of phosphorylated Erk and activated the Elk-1 transcription factor in human embryonal kidney 293 cells, suggesting that Depp modulates the effects of progesterone during decidualization and in the decidua by affecting gene expression. Elucidation of the biological function of Depp in the endometrium will facilitate our understanding of the molecular mechanisms of decidualization and placental development.