The susceptibility of normal, healthy children to infection has long been recognized, but the underlying mechanisms are poorly understood. As adequate cytokine production is crucial for optimal immune responses, we assessed antigen and mitogen-induced cytokine production in healthy children. Our results demonstrate that healthy children differ markedly compared with adults in their ability to produce cytokines (IL-2, interferon-gamma, IL-4, and IL-6). Maximal stimulation with mitogen demonstrated impaired cytokine production with markedly lower levels of all four cytokines produced compared with adult levels. When stimulated with antigens, median levels of IL-2 and IL-4 remained lower than adult values, IL-6 production was increased as was interferon-gamma, albeit not significantly. Although the study was carried out on peripheral blood mononuclear cells that represent a restricted compartment of the immune system, these data suggest that, in healthy children, cytokine production is decreased and/or altered and could result in a suboptimal immune response, which could be one of the factors underlying increased susceptibility to infection in children.