Lactoferrin (LF) has been found in most biological fluids including amniotic fluid and cervical mucus in pregnant women and is released from neutrophils in response to inflammation. It is an important component of the host defence against microbial infections due to its antimicrobial properties. Premature labour is caused by amniotic infection and high concentrations of inflammatory cytokines in amniotic fluid with infection are well established. In the present study, LF levels of intrauterine infection in amniotic fluid were measured and the biological significance of LF was investigated. The effects of LF on IL-6 production in cultured amnion cells were also investigated. The concentrations of LF and IL-6 in amniotic fluid with chorioamnionitis (CAM) were 8.76+/-0.65 microg/ml and 6.92+/-4.88 ng/ml (n = 28), respectively, and both were significantly higher (P<0.01) than those without CAM (0.86+/-0.81 microg/ml and 0.34+/-0.25 ng/ml; n = 31). LF and IL-6 levels were significantly higher (P<0.01) with CAM. A significant positive correlation between LF and IL-6 levels in amniotic fluid was found (r = 0.91, P<0.01). To our knowledge, this was the first study of its kind, which shows that IL-6 production induced by lipopolysaccharide in cultured cells was significantly inhibited below physiological concentration of LF in the amnion. In addition, the immunohistochemical localization of LF in fetal membranes was investigated. In the fetal membranes with CAM, strong positive staining was observed in amniotic and chorionic membranes, with leucocyte migration, while weak staining was observed in membranes without CAM. These results show conclusively that LF suppresses amniotic IL-6 production under the conditions of intrauterine infection.