Background: The autocrine, paracrine and hormonal effects of osteopontin (OPN), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) suggest that these cytokines may play key roles at the maternal-fetal interface. This study was performed to determine the effects of mifepristone on OPN, LIF and IL-6 mRNA and protein expressions in the villi in early pregnancy. Study Design: Twenty-nine healthy women seeking termination of pregnancy up to 40 days' gestation were recruited. The study group (n=14) was given 150 mg mifepristone 24 h before vacuum aspiration. The control group (n=15) was not given any treatment prior to vacuum aspiration. Villi were collected, and immunohistochemical analysis and real-time reverse transcription PCR (RT-PCR) were used to detect the locations and the expression levels of OPN, IL-6 and LIF mRNA. Results: In the study group, the expression level of OPN protein in the villous trophoblast and stoma cells was significantly lower (p<.01), while the expression levels of IL-6 and LIF protein were significantly higher than those in the control group (p<.01, p<.05, respectively). Compared with the control group, the relative expression of OPN mRNA was significantly lower (p=.001) and the IL-6 and LIF mRNA expression levels were significantly higher in the study group (p=.003 and p<.001, respectively). Conclusion: OPN, IL-6 and LIF may have critical roles in human pregnancy maintenance. These three factors may be involved in the immunological reaction initiated by mifepristone. © 2010 Elsevier Inc. All rights reserved.