Allergic respiratory inflammation in target organs does not occur in any atopic (genetically susceptible) subject, since other not fully characterized factors can influence the subsequent development of overt clinical disease. Here the Authors present some recent research developments that, together with some data coming from experimental animal models, can offer a “non-classical” interpretation about the way by which allergens are recognized and allergic inflammation persist. These aspects of the immunopathogenesis of allergic diseases can now be viewed as organ-specific pathways, acting independently from other peripheral lymphoid organs. This is a consequence of new knowledges about the function of, and molecular interactions by, intraepithelial γδ T cells and CD1⁺ dendritic cells. The allergic subject, unlike the normal one, is equipped at the mucosal surface by particular T-cells and APC subsets that recognize undenatured proteic and non-proteic (glycolipidic) external structures of aerodispersed particles, presented in the context of CD1 molecules. Other molecules on the surface of APC, like B7-2, contribute to the local activation of the allergen-specific T cell. Once initiated, the mucosal allergic reaction cannot be turned off in atopic individuals, because allergen-specific T cells lack surface Fas receptor and Fas mRNA. This defect, that impairs the so-called activation-induced programmed cell death (determined by Fas/FasL interaction), is caused by the local Th2-type cytokine milieu. In particular, GM-CSF, IL-5 and IL-4 are able to down-modulate, in a dose-dependent manner, Fas mRNA on purified cultured T lymphocytes. Thus, local cytokine concentration may prolong the survival of inflammatory cells in the lung of allergic subjects.