Objective: Several growth factors and cytokines appear to participate in the proliferation or differentiation of trophoblast cells. The purpose of this study was to investigate the extent to which keratinocyte growth factor participates in the development of human embryonic and trophoblast cells at the maternal-fetal interface. Study Design: The reverse transcriptase–polymerase chain reaction method was used to determine the gene expression of keratinocyte growth factor and keratinocyte growth factor receptor in human choriocarcinoma cells (BeWo), human teratocarcinoma cells (PA-1), and human endometrial stromal cells. We also examined the effects of keratinocyte growth factor on cell proliferation and production of human chorionic gonadotropin in BeWo and PA-1 cells. Results: Keratinocyte growth factor gene was expressed in all cell types. The expression was pronounced in stromal cells of the endometrium collected during the secretory phase and early pregnancy. The keratinocyte growth factor expression was also enhanced in the differentiated BeWo cells. The expression of keratinocyte growth factor receptor gene was observed only in the BeWo cells. The addition of keratinocyte growth factor to the medium did not affect cell proliferation of the BeWo and PA-1 cells. On the other hand, keratinocyte growth factor (100 ng/mL) significantly enhanced human chorionic gonadotropin production in the BeWo cells. Stimulatory action of keratinocyte growth factor on human chorionic gonadotropin production in the BeWo cells was markedly enhanced after forskolin-induced differentiation. Conclusions: We conclude that keratinocyte growth factor may play an important role in promotion of human chorionic gonadotropin production in the trophoblast cells. (Am J Obstet Gynecol 2000;182:692-8.)