Objective: The purpose of this study was to better understand the relationship between placental polymorphonuclear and mononuclear cell infiltrations with bacterial cultures, markers of inflammation, and preterm outcomes. Study design: This was a prospective study in 446 women who were delivered of a singleton infant at <32 weeks of gestational age. Five placental sites were categorized as having polymorphonuclear or mononuclear infiltrations. Results were compared with placental and cord cultures, umbilical cord interleukin-6 levels, and neonatal outcomes. Results: Polymorphonuclear, but not mononuclear, cell infiltrations were more common at the earliest gestational ages and in black women (56.0% vs 39.3%; P < .01). Polymorphonuclear infiltration was associated with spontaneous preterm birth (73.9% vs 8.0%; P < .0001), but not with preeclampsia (9.9% vs 34%; P < .0001). Women with positive cultures, high interleukin-6 levels, and clinical chorioamnionitis all had significantly more polymorphonuclear infiltrations than did women without those conditions (all probability values, <.0001). In all sites, polymorphonuclear infiltration was associated with neonatal systemic inflammatory response syndrome (P < .0001) and in the cord with necrotizing enterocolitis (22.4% vs 13.5%; P = .02). Intraventricular hemorrhage and neonatal death were not associated with polymorphonuclear infiltration. Polymorphonuclear infiltration at all sites was associated with less respiratory distress syndrome (P < .01). Mononuclear cell infiltration, when present in the decidua basalis, was associated with an increase in neonatal intraventricular hemorrhage (23.8% vs 7.4%; P < .0004). Plasmacytic infiltrates were associated with increased intraventricular hemorrhage (29.4% vs 8.3%; P = .01) and neonatal death (27.8% vs 9.2%; P = .02). Conclusion: Polymorphonuclear infiltrations of the free membranes, chorionic plate, and umbilical cord were associated with positive intrauterine cultures and elevated cord blood interleukin-6. There was also an association with systemic inflammatory response syndrome and necrotizing enterocolitis, but not with intraventricular hemorrhage or death, and with decreased respiratory distress syndrome. Decidual mononuclear cell infiltration was associated with an increased risk of intraventricular hemorrhage and decidual plasma cell infiltration with increased intraventricular hemorrhage and neonatal death. © 2006 Mosby, Inc. All rights reserved.