Over the past 15 years, it has become very clear that the immune system can have profound effects on epithelial function. Acute immune-mediated changes in epithelial physiology are beneficial to host defense against enteric pathogens. For example, ion secretion washes out noxious luminal contents and increased permeability allows phagocytic cells and antibodies to enter the gut lumen. However, ongoing immune activation results in chronic effects that may be pathophysiologic. Responses are mediated by soluble immune mediators that act directly on the epithelium, or indirectly via nerves that also serve to amplify the epithelial response. Here, we will review some of the recent advances that have been made in the field of immunophysiology. The effect of mast cells on transport functions of the epithelium will be reviewed, with emphasis on the consequence of interactions between mast cells and nerves. The use of in vitro coculture systems has recently provided considerable information on the effects of neutrophils, eosinophils, monocytes, and lymphocytes on epithelial functions; the contribution of each immunocyte will be highlighted. Finally, we will describe evidence for the active participation of the epithelium in mucosal immune activation, including pathogen or cytokine induced epithelial cytokine synthesis or secretion and adhesion molecule expression.