In order to clarify a regulatory mechanism of epidermal growth factor (EGF) in the decidualization process, EGF gene expression, the change in EGF receptor, and the cell proliferative effect of EGF in the human endometrium/decidua were assessed in both in vivo and in vitro decidualization systems. Northern blot hybridization showed that, although no hybridized band was found in the proliferative and secretory phase endometria, a specific band of 5 kb was detected in decidua of early pregnancy as well as in in vitro medroxyprogesterone acetate-induced decidual cells. In situ hybridization revealed that prepro-EGF mRNA was observed in the stromal cells of decidua. Scatchard plot analysis of 125I-EGF-binding studies for the homogenates from these endometria/ decidua revealed that its binding sites increased in accordance with the decidualization process, and its dissociation constant remained unchanged. EGF had a stimulatory action on cell proliferation in the early pregnant decidual cells. These results demonstrate that EGF production, EGF receptor, and decidual cell growth increase in accordance with the process of decidualization, suggesting that EGF may play an important role in the regulation of decidualization in human endometrium through an autocrine/paracrine system.