Dendritic cells (DCs) and epithelial cells are the first cells to encounter inhaled allergens. The response of these cell types to allergens is fundamentally different in asthmatics compared with nonasthmatics. DCs and epithelial cells interact through cell-cell interactions and through release of soluble mediators. The response of epithelial cells to allergens can profoundly modify the behavior of intramucosal DCs. Upon migration to the draining nodes, mucosal DCs undergo functional maturation and induce proliferation in naive T cells and primed Th2 cells. The implications of the DC-epithelial interaction for the pathogenesis of asthma is becoming increasingly clear by the use of mouse models and culture systems of human cells.