Electrophysiological studies have determined the fundamental mechanisms underlying fluid and electrolyte transport by the pancreatic duct cell. Stimulated fluid and bicarbonate secretion by these cells involves activation of an apical membrane chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR). The intracellular protons that accumulate during this process are extruded basolaterally, possibly by proton pumps inserted into the plasma membrane. Although secretion is clearly regulated by secretin and the cyclic AMP pathway, it is apparent that other agents (acetylcholine, bombesin, and substance P), acting through calcium and other pathways, can also regulate the process. With the exception of CFTR, however, the sites of regulation have not been completely established. As a target of both protein kinase A and protein kinase C, CFTR is one potential site for regulation by different signaling pathways. Furthermore, CFTR may have intracellular functions, raising the possibility that its activation affects additional duct cell processes.