This chapter focuses on the dendritic cells (DCs) and macrophages in the intestine and respiratory tracts, as these organs constitute the major mucosal surfaces of the body. DCs can be divided into follicular and nonfollicular DCs. The mucosal DCs have a particular capacity to induce regulatory T-cell differentiation in the steady (noninfected, nonimmunized) state, but allow for the induction of effector T-cell responses-depending on both the particular subpopulation involved and the surface receptors engaged during the DC activation and T-cell priming. The mucosal DCs contribute to innate defense-by production of cytokines, such as type 1 interferons (type 1 IFNs) and interleukin-12 (IL-12), following the direct exposure to pathogens, as well as contribute to the maintenance of secondary T-cell responses within inflamed mucosa. Resident intestinal macrophages have unique functions as they do not appear to act as antigen-presenting cells (APCs) or produce inflammatory cytokines, but avidly scavenge, phagocytose, and kill pathogens and macromolecules. Thus they are noninflammatory specialized cells for mucosal defense against pathogens. © 2005 Elsevier Inc. All rights reserved.