Increasing evidence supports the view that infants exposed to perinatal infection are at increased risk for brain injury. We suggest that elevated cytokines in the amniotic fluid or in the fetal circulation be viewed as a humoral expression and that inflammatory cells in chorionic plate or umbilical cord blood vessel walls be viewed as a morphologic expression of the fetal inflammatory response. We discuss the evidence supporting the hypothesis that the fetal inflammatory response contributes to neonatal brain injury and later developmental disability. Little support has been found for a maternal contribution. Intervention should be designed with the fetus in mind.