This review discusses recent findings regarding the mechanisms and regulation of chloride secretion in the T84 cell line, a widely used model for the study of transepithelial chloride transport, the properties of the cystic fibrosis gene product (cystic fibrosis transmembrane conductance regulator), and the interactions of inflammatory cell types with the intestinal epithelium. First, I review the features of the chloride secretory mechanism in this cell line, both as originally described by Dharmsathaphorn and co-workers and as modified by more recent findings. Second, I cover what is known of the intracellular regulation of the secretory process. Third, I review the ways in which the cell line has been utilized to dissect pathways of immune-epithelial interactions that may contribute to the pathogenesis of inflammatory diarrhea. Finally, I suggest areas of investigation with this cell line that may prove ripe for further study. The physiological and pathophysiological implications of findings obtained with the cell line are also discussed.