Innate and adaptive immune responses to respiratory syncytial virus (RSV) in neonates were assessed by cord blood mononuclear cell (MC) cytokine expression and proliferation and these responses were compared with those from adult peripheral blood MCs. In adult cells, inactivated and live virus invoked cytokines reflecting both innate and adaptive immunity (interleukin [IL]-6, interferon [IFN]-gamma, IL-2, tumor necrosis factor [TNF]-alpha, and IL-10). Low levels of IL-4 were detected, although only with inactivated virus. In contrast, in neonatal cells, inactivated virus invoked large levels of the innate immune cytokines IL-6, TNF-alpha, and IL-10 and reduced levels of IFN-gamma and IL-12 but no adaptive cytokines. Live virus induced fewer innate (IL-6, IL-10, and IFN-gamma) and no adaptive immune cytokines. RSV-induced proliferation was absent in neonatal MCs, although positive in adult MCs. Thus, exposure to RSV does not appear to occur before birth, and adaptive immune insufficiency or greater innate responses may account for early life RSV-induced illnesses.