Only recently has it been recognized that intracellular Ca2+ 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 Ca2+. This effect was fast, reversible, dependent on the extracellular Na+ concentration and did not correlate with intracellular pH changes. It was abolished in Ca2+-free solutions, indicating that the outwardly directed Na+ gradient was directly coupled to a flufenamate insensitive Ca2+ influx. Removal and reintroduction of extracellular Na+ induced transient hyperpolarization and depolarization of Vm, respectively. Taken together, our data indicate that pancreatic ducts possess an electrogenic Na+-Ca2+ exchanger, which under control conditions is responsible for transporting Ca2+ out of resting duct cells.