The development of childhood asthma and/or atopy has been associated with the persistence of T-helper type 2 (Th2) cytokine responses. Diminished interleukin-10 (IL-10) production from dendritic cells (DCs) may influence Th2 skewing. The purpose of this study was to characterize the ontogeny of DC IL-10 and Th2 responses during infancy. Blood was obtained from 40 healthy infants at 2 weeks, 3 months, and 5 months of age, and from 20 healthy children aged 6-12 years. Peripheral blood mononuclear cells (PMNCs) were purified and stimulated, and supernatants were assayed for IL-13 and IFN-␥. DCs were cultured and stimulated, and supernatants were assayed for IL-10. Median DC IL-10 (pg/mL) and Th2 cytokine production (IL-13:IFN-␥) were 1.5 and 2.6 at 2 weeks, 1.5 and 2.9 at 3 months, 1.5 and 3.0 at 5 months, and 11.0 and 0.9 during childhood, respectively (p Ͻ 0.01). The frequency of subjects with detectable IL-10 levels was 28% at 2 weeks, 18% at 3 months, 19% at 5 months and 85% during childhood (p Ͻ 0.001). These results demonstrate that DC IL-10 production is diminished and Th2 skewing is enhanced during infancy. Future studies need to expand upon the sample size and determine whether diminished DC IL-10 production during infancy predisposes to the development of asthma and/or atopy.