Interleukin (IL)-27, a heterodimer composed of Epstein-Barr virus-induced gene 3 (EBI3) and p28, is an early product of activated dendritic cells (DC). Binding of IL-27 to the WSX-1 receptor initiates Th1 (Thelper 1) responses in naïve T cells. In order to assess the Th1 responses in human neonates with high susceptibility to infectious diseases, expression of EBI3-, p28- and WSX-1-mRNA in response to Toll-like receptor ligands was compared in neonate and adult monocyte-derived (m)DC. Only the combined addition of ligands induced expression of IL-27p28 mRNA. Surprisingly, neonatal mDC produced significantly more IL-27p28 mRNA than that obtained from adults. Furthermore, there was enhanced expression of EBI3 mRNA in cord blood as compared with adult blood. In addition, the secretion of WSX-1 mRNA in neonatal mDC and T cells was also significantly increased. Taken together, these findings indicate that the restricted Th1 responses in human newborns owing to deficient IL-12 production may be compensated for, in part, by enhanced IL-27 secretion.