Cultured oligodendrocytes take up K+ triggered by an increase in [K+]o. Simultaneously [Cl−]i increases in the majority of the oligodendrocytes. This KCl uptake, which is not furosemide sensitive, can be explained by the following model. The first event is the entry of Cl− into the cell driven by the discrepancy between the membrane and Cl− equilibrium potential. As a consequence of the movement of negative charge across the membrane, K+ is driven into the cell. The prerequisites of this model, a passive Cl− distribution at resting membrane potential and a Cl− conductance of the membrane were found to exist in most cultured oligodendrocytes. The chloride equilibrium potential (−61 mV, SD ± 10 mV) was slightly more positive than the membrane potential (−64 ± 8 mV), Since cell input resistance determined with two independent electrodes increased by 11% (SD ± 0.07) when [Cl−]o was reduced to 10 mM, part of the membrane conductance appears to be mediated by Cl−. Differences between membrane potential and Cl− equilibrium potential therefore will lead to Cl− fluxes across the membrane. In contrast with oligodendroyctes, [Cl−]i in astrocytes is significantly increased (from 20 to 40 mM) above the equilibrium distribution owing to the activity of an inward directed Cl− pump; this suggests a different mechanism of K+ uptake in these cells.