We have studied outward currents of neurons acutely isolated from superficial layers of the entorhinal cortex with whole-cell patch-clamp recordings. If cells were held more negative than -50 mV, depolarizing voltage commands activated a transient A-type current together with a sustained outward current. Both currents were sensitive to 4-aminopyridine, while only the sustained current was blocked by tetraethylammonium. The sustained outward current showed a considerable rundown in amplitude over prolonged recording periods. At the same time its half-maximal inactivation shifted from -74 to - 114 mV. Nystatin perforated patch recordings were used to minimize these perfusion effects. Under such conditions the amplitude and the steady-state inactivation properties of the sustained outward current remained stable for more than 1 h. Pharmacological investigations revealed that only a small part of the sustained outward current could be attributed to a calcium-activated potassium current. Therefore most of the rundown has to be due to changes in the delayed rectifier outward current. These results may suggest that the delayed rectifier current is under considerable metabolic control.