We describe, for the first time, a potassium current in acutely isolated mouse pancreatic acinar cells. This current is activated by depolarization and has many of the characteristics of the fast transient potassium current of neurones where roles in shaping action potential duration and frequency have been proposed. Although acinar cells do not carry action potentials, our experiments indicate that the primary regulator of the current in these cells is the membrane potential. In whole-cell patch-clamped cells we demonstrate an outward current activated by depolarization. This current was transient and inactivated over the duration of the pulse (100 - 500 ms). The decay of the inactivation was adequately fitted by a single exponential. The time constant of decay, τ, at a membrane potential of +20 mV was 34 ± 0.6 ms (mean ± SEM, n = 6) and decreased with more positive pulse potentials. The steady-state inactivation kinetics showed that depolarized holding potentials reduced the amplitude of the current observed with a half-maximal inactivation at a membrane potential of -40.6 ± 0.33 mV (mean ± SEM, n = 5). These activation and inactivation characteristics were not affected by low intracellular calcium (10-10 mol · l-1) or by an increase in calcium (up to 180 nmol · l-1). In addition we found no effect on the current of dibutyryl cyclic adenosine monophosphate (db-cAMP) or the agonist acetylcholine. The current was blocked by 4-aminopyridine (K(d) approximately 0.5 mmol · l-1) but not affected by 10 mmol · l-1 tetraethylammonium. Whole-cell patch-clamp experiments were also carried out on acutely isolated mouse lacrimal acinar cells. Depolarizing voltage-clamp steps elicited only a slowly activating outward current that was blocked by tetraethylammonium. We found no evidence for the fast transient outward current in the exocrine cells of the lacrimal gland. We postulate that the transient potassium current in the acinar cells of the mouse pancreas would act to hyperpolarize the cell and may play a role in fluid secretion.