Background: Dendritic cells are antigen-presenting cells central to the immune system. They activate and orchestrate the innate and the adaptive immune systems. This phenotypically diverse group can be further divided into 2 subsets, the CD11c+ myeloid dendritic cells (mDCs) and the CD123+ plasmacytoid dendritic cells (pDCs). The aim of the study was to investigate the effect of allergen exposure on dendritic cells in subjects with allergic rhinitis. Methods: Atopic and non-atopic subjects were challenged intranasally with birch or timothy allergen. Nasal biopsies were taken before and 24 h after challenge, and were, after CD68 exclusion, stained for expression of CD11c and CD123 to identify dendritic cell subsets. The effect of allergic mediators on CD68–,CD123+ cells was studied with flow cytometry analysis in peripheral blood. Results: The amount of CD68–,CD123+ cells increased in the nasal sub-epithelium upon allergen challenge, whereas the number of CD68–,CD11c+ cells was unaffected. In vitro study of the effect of inflammatory mediators on pDC phenotype showed an increased activation in response TNF-α, IL-4 and CpG. Furthermore, TNF-α caused a higher activation among atopic than non-atopic subjects. Conclusions: An increased number of CD68–,CD123+ dendritic cells along with the positive pDC response following stimulation with inflammatory mediators suggest that the increased pDCs may be of an activated phenotype. It also suggests that the inflammatory response by pDCs to mediators such as TNF-α may be markedly higher in atopic subjects. These data support the notion of pDCs as important participants in allergic rhinitis.