IL-10 is regarded predominantly as an inhibitor of cell-mediated inflammatory reactions. As much, it has been suggested that IL-10 could have therapeutic potential, including the treatment of preterm labor. Using explant cultures of gestational membranes we have found that IL-10 does indeed exert anti-inflammatory properties in choriodecidua, but that in the adjacent amnion it has remarkable pro-inflammatory actions. Amnion prostaglandin (PG) E-2 production was significantly increased following 24-h treatment with IL-10 (5-100 ng/ml). Production of IL-8 also showed a significant stimulation at 100 ng/mL IL-10. In contrast, choriodecidual production of IL-8 and tumor necrosis factor (TNF)-alpha was dramatically inhibited by IL-10, confirming the ability of this tissue to exhibit a classical IL-10 response IL-10 retained its stimulatory actions on amnion in the presence of IL-1beta and TNF-alpha stimulation. These findings suggest that the fetal membranes can exhibit opposing responses to IL-10, depending on whether the inflammatory insult occurs at the maternal or fetal face. While inflammatory reactions are negatively regulated by IL-10 in choriodecidua, if the pathogen reaches the amnion and threatens the fetus, pro-inflammatory reactions may predominate to ensure successful labor to spare and protect the fetus.