Rationale: Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. Objectives: It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust-derived PM affects dendritic cell (DC) activation. Methods: DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). Measurements: DC were stimulated for 48h with CEP, DEP, CD40-ligand or lipopolysaccharide. DC activation was assessed by flow cytometry, ELISA and standard culture techniques. Results: DEP increased uptake of FITC-dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g. CD40 (P<0.01) and MHC class II (P<0.01). By contrast, CEP poorly affected antigen uptake, expression of cell surface molecules and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6 and IFN-gamma (P<0.01), IL-12 (P<0.05) and vascular-endothelial growth factor (P<0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g enhanced IL-13 and IL-18 and suppressed IFN-gamma production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Conclusion: Car- and diesel-enriched particles exert a differential effect on DC activation. Our data supports the hypothesis that DEP and to a lesser extent car particles) regulate important functional aspects of human DC, supporting an adjuvant role for this material.