Age-associated dysregulation of the immune system of the gastrointestinal (GI) tract has been well documented for both secretory (S)-IgA immunity and oral tolerance. Thus, impaired antigen-specific Ab responses in aged animals and the elderly have been reported. Further, it has been shown that gut-associated lymphoreticular tissue (GALT) mediated immune responses are more susceptible to aging than are lymphoid tissues involved in peripheral immunity. Aging also impairs oral tolerance, which may be of central importance for maintaining GI homeostasis. Thus, as early as 6-8-month-old mice failed to establish systemic unresponsiveness to orally introduced antigens. Despite these studies, the precise mechanisms for impaired GI tract immune system responses remain unclear. The evidence of reduced sizes of Peyer's patches through aging suggests that age-associated mucosal dysregulation may be the result of mucosal inductive tissue dysfunction. Indeed, the frequencies of naïve CD4+ T cells and dendritic cells (DCs) in Peyer's patches of aged mice were reduced and this led to a lack of essential cytokine synthesis for the induction of either S-IgA immunity or oral tolerance. © 2004 Elsevier Ireland Ltd. All rights reserved.