SUMMARYThe perforated patch technique was used to study the effects of hypotonic extracellular solutions on membrane potential and whole-cell currents in intact rat pancreatic ,l-cells. A 30 % reduction in osmolarity resulted in activation of an outwardly rectifying CF-selective conductance in rat f-cells. This conductance was inhibited by the anion channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS). Exposure to a hypotonic medium also led to a transient stimulation of electrical activity accompanied by cell swelling and a gradual return towards control volume. These effects were also associated with the generation of an inward current at a holding potential of -70 mV, and a stimulation of insulin release from intact perifused islets. All of the above effects were inhibited by DIDS. It is suggested that the stimulation of insulin release by hypotonic solutions results from activation of a volume-sensitive anion conductance generating an inward current and leading to a subsequent depolarization of the ,-cell.