As mucosa-associated lymphoid tissues, nasopharyngeal-associated lymphoreticular tissues (NALT) and Peyer's patches (PP) are key inductive tissues for the generation of antigen-specific mucosal immune responses via the respiratory and intestinal tracts, respectively. In this study, we have established that both the IL-7R-and LTβ receptor (LTβR)-mediated cytokine-signaling pathways are essential for the tissue organogenesis of PP by demonstrating that the blockage of the LTβR signaling cascade by in utero treatment with the LTβR-Ig fusion protein resulted in deficient PP formation. Further, in utero co-administration of LTβR-Ig with TNFR-Ig resulted in the lack of both PP and mesenteric lymph node (MLN) formation. Our findings also constitute new evidence that NALT requires its own set of cytokines and its own cytokine receptor cascade. In contrast to organogenesis in PP and in other secondary lymphoid tissues, NALT formation does not appear to be dependent on the IL-7R and LTβR signaling pathways, known as the essential cytokine cascade. Instead, a population of inducer cells with a phenotype of CD3−CD4+CD45+ was found to be responsible for the initiation of NALT organogenesis. These findings demonstrate that the lymphoid tissue organogenesis of the respiratory tract relies on a distinct set of cytokine/cytokine receptor-signaling cascades from organogenesis in the digestive tract.