The effect of secretin on glucagon and insulin release and its interaction with glucose has been studied in cultured mouse pancreatic islets by column perifusion. Glucose alone showed the well-known stimulation of insulin release and inhibition of glucagon release. Addition of 10 mM secretin increased glucagon secretion at 3 mM D-glucose by 300% while no change in insulin release could be seen at this low glucose concentration. At maximal stimulation of insulin release by 20 mM D-glucose addition of 10 nM secretin increased insulin release by 30%. Despite this insulin concentration and the high glucose concentration an increase in glucagon secretion of 1800% was found. These effects of secretin were dose-dependent at 10 mM D-glucose with 1 nM secretin being the lowest effective dose.