PROBLEM: The aim of this study was to clarify the physiological effects of interferon (IFN)-gamma on secretion of vascular endothelial growth factor (VEGF) by endometrial stromal (ES) cells. METHOD OF STUDY: ES cells were obtained from human uterine endometrium by enzymic digestion and filtration. The effects of IFN-gamma on production of VEGF by ES cells were examined by analyzing VEGF mRNA expression with Northern blotting analysis and by assaying VEGF protein. RESULTS: IFN-gamma inhibited VEGF mRNA and protein expression by ES cells in a dose-dependent manner. In ES cells treated with IFN-gamma, VEGF production was not significant until 6 hr of incubation and was significantly affected after 6 hr of incubation, but decreased significantly after 12 to 48 hr. IFN-gamma also suppressed VEGF mRNA expression by ES cells. CONCLUSIONS: ES cells produce VEGF, which may contribute to endometrial neovascularization and proliferation. IFN-gamma may play an important role in regulating VEGF production by ES cells.