Only recently has it been recognized that intracellular Ca*+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted in a significant increase in intracellular Ca '+. This effect was fast, reversible, dependent on the extracellular Na+ concentration and did not correlate with intracellular pH changes. It was abolished in Ca*+-free solutions, indicating that the outwardly directed Na+ gradient was directly coupled to a flufenamate insensitive Ca*+ influx. Removal and reintroduction of extracellular Na+ induced transient hyperpolarization and depolarization of V,,,, respectively. Taken together, our data indicate that pancreatic ducts possess an electrogenic Na+-Ca*+ exchanger, which under control conditions is responsible for transporting Ca*+ out of resting duct cells.