Normal turnover of body tissues yields apoptotic cells while infections cause tissue injuries and cell necrosis. The interaction of these dying cells with dendritic cells (DCs) may provide immunological instructions leading to either immune tolerance or activation. We hypothesize that neonatal and adult DCs differ in their responses to dying cells, thereby contributing to the observed differences in immune responses between neonates and adults. We compare the outcome of interaction of cord and adult blood-derived DCs with dying Epstein-Barr-virus-transformed lymphoblastoid cells (LCLs) and the responsiveness to lipopolysaccharide. While cord DCs were able to phagocytose both apoptotic and necrotic LCLs, the subsequent responses differed significantly from those of adult DCs. Interaction of adult DCs with necrotic but not early apoptotic LCLs resulted in high expression of DC costimulatory molecules (CD80/CD86) and activation markers (CD83), production of both proinflammatory and anti-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-10), and strong T-cell-stimulating activities. In contrast, in response to either necrotic or apoptotic LCLs, cord DCs had minimal up-regulation of those DC functional markers, little cytokine production and poor stimulation on T-cell proliferation. In response to lipopolysaccharide, however, both adult and cord DCs produced comparable levels of tumour necrosis factor-alpha and interleukin-10, but only adult DCs produced interleukin-12(p70). Taken together, these results suggest that neonatal DCs generally favour immune tolerance with minimal activation and cytokine production, except in extremely dangerous situations, such as bacterial sepsis, when neonatal DCs may produce certain types of cytokines and stimulate T-cell proliferation.