The intestine is a unique immunologic organ that comprises an afferent and efferent compartment and provides the host with the ability to respond through several different effector mechanisms against environmental factors. We discuss mechanisms in three intestinal diseases in this overview of the mucosal immune system. Genetic and immunologic factors are important in the pathogenesis of celiac disease, which is characterized by damage to the mucosa of the small intestine with resultant malabsorption. Pathogenic microbes are important environmental agents that interact with the intestinal mucosa and initiate local immune responses. Advances in the understanding of the mucosal immune response to these pathogenic microbes have produced a clear picture of the way in which this specialized immune system works in concert with systemic immunity. As to the autoimmune nature of inflammatory bowel disease, no specific antigen has been shown to incite the inflammatory reactions and neither the target cells nor the effector mechanism involved have been identified. Several factors exist, however, to suggest an autoimmune mechanism and the role of mucosal immunologic factors in this disease.