The intestinal epithelium is an important site of active solute transport processes. Such processes include the secretion of electrolytes into the lumen, predominantly chloride and bicarbonate. These secretory mechanisms subserve a variety of functions, both physiological and pathophysiological, including maintenance of the fluidity of intestinal contents and mucosal defense. Both chloride and bicarbonate secretion are the subject of integrated regulatory mechanisms at both the intercellular and intracellular levels. The goal of this article is to discuss data that exemplify these two levels of regulation, which have been the subject of research in my laboratory. It is likely that some of these principles are also broadly applicable to secretory epithelial cells outside of the intestinal tract, such as those in the airway. I also discuss the ways in which we believe these regulatory mechanisms are involved not only in intestinal physiology but also perhaps in the pathogenesis of specific disease states.