Acinar cell membrane potentials and amylase release were measured from in vitro preparations of mouse pancreas. The effect of a 10-fold increase of the extracellular K⁺ concentration (to 47 mM) was studied on the resting membrane potential and amylase release as well as on the membrane depolarization and amylase release induced by the cholecystokinin-pancreozymin analogue, caerulein. In the presence of atropine (to exclude the effect of a possible release of endogenous acetylcholine), the increased K⁺ concentration depolarized the cells from −45 to −20 mV without influencing the rate of the unstimulated release of amylase. Under these conditions, the depolarizing effect of caerulein was almost abolished, while the caerulein-induced amylase was not. It is concluded that caerulein-induced enzyme secretion from pancreatic acinar cells is independent of the level of the membrane potential as well as extracellular K⁺ concentration in the range from 4.7–47 mM.