Interleukin 1 (IL-1) is known to be present in placental tissue and is implicated as an endogenous mediator of inflammation and parturition. This study was undertaken to assess the role of IL-1 receptor antagonist (IL-1ra) in the placenta. Placentas with acute chorioamnionitis, with meconium staining, and without significant inflammation were examined for immunohistochemical expression of IL-1 and IL-1ra. Interleukin 1 and IL-1ra immunoreactivity was variably noted in the amnion, trophoblast, vascular smooth muscle, stromal cells, fibrinoid, and decidua in all placentas. Interleukin 1 immunoreactivity was less intense than IL-1ra immunoreactivity, and both were generally more intense in acute chorioamnionitis. Interleukin 1 receptor antagonist was detected (approximately 5 to 6 ng/mL) in the amniotic fluid of pregnant women at term. Colocalization of IL-1 and IL-1ra in normal and inflamed placentas suggests that the balance between these proinflammatory and anti-inflammatory mediators plays a role in parturition as well as in the pathogenesis of acute inflammation. An increase and/or imbalance in the IL-1 and IL-1ra expression associated with chorioamnionitis may precipitate preterm labor.