The cause of intrauterine growth restriction (IUGR) with abnormal umbilical artery (UA) Doppler indices is unknown. Previous studies indicate rearrangement of placental villi occur in IUGR pregnancies, disturbing normal blood flow to the developing fetus. Vasculature integrity is regulated by a variety of factors, including inflammatory cytokines. Inflammatory factors interleukin 6 (IL6), IL8, and CCL2 have been implicated in abnormal placental structure and function in pre-eclamptic and hypertensive mothers. We determined expression of cytokines IL8, IL6, TNFα, and CCL2 in placentae with abnormal UA Doppler IUGR. Fetuses diagnosed with IUGR (weight <10%) and abnormal UA Doppler indices (increased systolic:diastolic ratio, absent, or reversed end diastolic flow) were compared to fetuses with normal parameters. Placentae were collected from IUGR and control (normally-grown) subjects from both singleton and multiple pregnancies. For singletons, IUGR (n=7) and controls (n=5) were unrelated. For multiple pregnancies, IUGR fetuses (n=4) were compared to the normally-grown control fetuses (n=5) from the same pregnancy. At delivery, one central and four peripheral 3 mm biopsies were collected and stored. RNA was isolated. IL6, IL8, CCL2, and TNFα mRNA expression was determined with quantitative PCR. In singleton pregnancies, IL8 was significantly (P<0.05) increased in IUGR placenta. IL6, TNFα, and CCL2 were not differentially expressed in singletons. In multiple pregnancies, IL6 was significantly (P<0.05) decreased in IUGR placenta, while other genes were not differentially expressed. These data establish a role for interleukins in IUGR placenta. Although a causal relationship is not yet established, the increase in IL8 in IUGR placenta is consistent with inflammation that may contribute to poor placental development. IL6 has both pro and anti-inflammatory functions and the decrease seen in IUGR placenta from multiple gestations proposes non-genetic origins of the IUGR pathology.