We investigated whether histological chorioamnionitis (HCA) is a risk factor predisposing to leukemoid reaction (LR) and whether LR is associated with the preterm parturition syndrome and the systemic fetal inflammation response syndrome. A prospective histological study on placentas was performed in preterm infants (<or=32(+6) weeks' gestation) admitted to level III neonatal intensive care unit of Padua University from January 1998 to December 2003. Development of LR was related to evidence of HCA. Among the placentas of the 223 preterm examined infants, 61 (27%) were diagnosed with HCA. Overall incidence of LR was 5.3%. Of 61 preterm neonates with HCA, 8 (13%) developed LR; moreover, 4 (2%) of 162 preterm infants without HCA developed LR (odds ratio = 7.4). Neonates with both LR and HCA differ from neonates with LR and without HCA in occurrence of prolonged rupture of membranes (62.5% versus 0%, P < .01), mode of delivery (37.5% versus 100% cesarean delivery, P < .01), gestational age (26 +/- 1.6 versus 29.7 +/- 1.7 gestational weeks, P < .01), and bronchopulmonary dysplasia incidence (63% versus 25%, P < .01). Histological chorioamnionitis placental findings increase the risk for neonatal LR. The LR in low-birth-weight neonates with HCA is significantly associated with earlier delivery and bronchopulmonary dysplasia. Pathogenetic mechanisms of neonatal LR in low-birth-weight infants without HCA remain undefined.