SLC26 (human)/Slc26 (mouse) isoforms are members of a large, conserved family of anion exchangers that display highly restricted and distinct tissue distribution. Cloning experiments have identified the existence of 10 SLC26 genes or isoforms (SLC26A1–11). Majority of these isoforms function as anion exchangers with versatility with respect to transported anions. Modes of transport mediated by SLC26 members include the exchange of chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, or oxalate with variable specificity. Several members of SLC26 family mediate chloride-bicarbonate exchange and display expression in the gastrointestinal tract, with distinct subcellular (apical or basolateral) localization. These include SLC26A3 (DRA), SLC26A6 (PAT1 or CFEX), SLC26A7 and SLC26A9. SLC26A7 and SLC26A9 can also function as chloride conductive pathways. SLC26A3 is expressed on the apical membrane of enterocytes in the small and large intestines whereas the expression of SLC26A6 (PAT1) is limited to the apical membrane of the small intestine. SLC26A7 and SLC26A9 are expressed in gastric epithelial cells, with SLC26A7 predominantly detected on the basolateral of parietal cells and SLC26A9 expressed in both parietal cells and mucus cells. SLC26A7 and A9 are not expressed in the intestine. Genetically engineered null mice have highlighted the important roles of these 4 isoforms in stomach or intestine physiology. Slc26a3 (DRA) deletion in mice recapitulates the phenotype of chloride losing diarrhea in human, an autosomal recessive disorder manifested by massive chloride and fluid loss in the stool after birth. Deletion of Slc26a6 (PAT1) impairs salt absorption and PGE-2 stimulated bicarbonate secretion in the small intestine. Both DRA and PAT1 are activated by luminal fructose and mediate enhanced salt absorption in the small intestine. Slc26a7 deletion impairs histamine-stimulated acid secretion in intact stomach and isolated gastric mucosae by 35–45% in 4–5 weeks old mice, with no detectable structural abnormality in light or electron microscopy. Slc26a9 deletion completely abrogates acid stimulation in intact stomach and in isolated gastric mucosae in 4–5 weeks old animals and causes reduction in gastric parietal cells, complete loss of tubulovesicles and rearrangement of actin cytoskeleton. In conclusion, Slc26a3, 6, 7 and 9 display distinct expression pattern in gastrointestinal tract and play essential roles in electrolyte absorption in the intestine or acid secretion in the stomach.