Although reports have been published on the generation of transforming growth factor-beta 1 (TGF-beta 1) and expression of TGF-beta receptors in human endometrial tissues, the biological functions of endometrial TGF-beta 1 have remained unclear. In this study, the effects of TGF-beta 1 on endometrial apoptosis were examined by using an endometrial epithelial cell line HHUA which is susceptible to Fas-mediated apoptosis. TGF-beta 1 alone did not affect the cell growth of HHUA, but pretreatment of HHUA with TGF-beta 1 enhanced Fas-mediated growth suppression and DNA fragmentation of the cells. Flow cytometric analyses showed that TGF-beta 1 did not affect Fas expression on the cell surface. These findings lead to the conclusion that TGF-beta 1 enhances susceptibility to Fas-mediated apoptosis in the endometrial epithelial cell. Modulation of Fas-mediated endometrial apoptosis by TGF-beta 1 may thus be a tissue-specific effect which is distinct from other TGF-beta 1 effects on Fas-mediated apoptosis in activated T-cells and rheumatoid synovial cells. The biological functions of endometrial TGF-beta 1 and endometrial apoptosis are also discussed.