This chapter discusses the mucosal immune system of the genitourinary tract. The chapter also discusses the significance of the mucosal immune system in the development of the fetus and neonate, including maternal-fetal interactions and major differences among species. Although the intestinal tract, as a typical locus of mucosal immune system function, and the urogenital system develop in parallel during embryogenesis and maintain anatomical proximity in postnatal life-their immunological characteristics show striking differences. In addition to S-IgA, urogenital IgA contains a considerable percentage of monomers. These features are relevant to inducing humoral immune responses in genital tract secretions. Through the homing properties of lymphocytes in the common mucosal immune system, oral and rectal immunizations yield S-IgA antibodies in most of the external secretions-including those of the female genital tract. For eliciting antibodies in genital secretions, the most effective route of immunization may be intranasal due to distinctive lymphocyte homing receptors and local chemokines involved in the selective population of the genital mucosae by cells originating from nasopharyngeal-associated inductive sites. © 2005 Elsevier Inc. All rights reserved.