The effects of four endometrial cytokines, transforming growth factor beta1 (TGF-beta1), interleukin-1beta (IL-1beta), epidermal growth factor (EGF), and hepatocyte growth factor (HGF), on Fas-mediated apoptosis in the human endometrial epithelial cell line, HHUA, were investigated. Although the cell growth of HHUA was not directly affected by TGF-beta1, IL-1beta, or EGF, pretreatment of HHUA with TGF-beta1, IL-1beta, or EGF enhanced Fas-mediated growth suppression and Fas-mediated DNA fragmentation in the cells. Flow cytometric analyses demonstrated that TGF-beta1, IL-1beta, and EGF did not induce Fas expression on the cell surface. These results suggest that TGF-beta1, IL-1beta, and EGF enhances apoptotic susceptibility of the cells. However, HGF inhibited Fas-mediated growth suppression and DNA fragmentation in the cells without any increase in Fas antigen expression on the cells. This finding suggests that HGF suppresses apoptotic susceptibility of the cells. From these results, we conclude that the endometrial cytokines may play a role in reshaping the endometrium after menstruation or in regulating apoptotic susceptibility in endometrial epithelium in the mid- to late-secretory period.