RANTES (regulated upon activation, normal T cell expressed and secreted), which is a potent chemoattractant for eosinophils, lymphocytes, and monocytes, was recently detected in the human endometrium. The effects of modulators of endometrial function, including lipopolysaccharide (LPS), tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-4 and interferon-gamma (IFN-gamma), on the production of RANTES by endometrial stromal cells (ESC) were examined by an enzyme-linked immunosorbent assay and Northern blot analysis. The concentration of RANTES in the culture media of non-stimulated ESC was below the level of detection. The concentration of RANTES was increased by the addition of TNF-alpha, IL-1 beta and LPS. IFN-gamma synergistically enhanced the TNF-alpha- and LPS-induced RANTES expression, but had no effect on the IL-1 beta-induced RANTES expression. The TNF-alpha-induced production of RANTES by ESC was inhibited by IL-4. The transcription of RANTES in ESC was also stimulated by TNF-alpha, IL-1 beta and LPS in a dose-dependent manner. It is suggested that the LPS and cytokines secreted by the maternal decidual tissue and the developing embryo may regulate the production of RANTES by ESC, The modulation of RANTES concentration in the local environment may contribute to the pathophysiological processes of human reproduction by regulating the immunological reaction at the fetal-maternal interface.