There is growing evidence that sepsis-related complications in neonates are crucially mediated by the action of proinflammatory cytokines. It has previously been demonstrated that elevated IL-6 and IL-8 levels can predict brain damage and chronic lung disease in preterm infants. However, it is the current view that neonates have a reduced capability to produce proinflammatory cytokines. To clarify this issue, we analyzed the inflammatory response in term and preterm infants directly at the single cell level by flow cytometry. Endotoxin challenge was performed under defined conditions on monocytes obtained from 50 healthy adults and 119 neonates, which consist of 45 term infants, 63 preterm infants (26.1–36.7 wk of gestational age), and 11 preterm infants with proven infection (24.6–29.9 wk). Our results challenge the existing view of an immature inflammatory response by demonstrating that term infants and preterm infants display a higher percentage of IL-6–and IL-8–positive cells than adults. After preincubation with dexamethasone the number of cytokine-positive cells decreased in all groups, but the number of IL-8–positive cells remained higher in term and preterm infants> 32 wk compared with adults. These observations demonstrate not only a well-developed but also an enhanced inflammatory response in term and preterm infants. Under consideration of several detrimental effects of IL-6 and IL-8, our data may have major implications on the pathophysiology of inflammatory-triggered neonatal diseases.