Abstract γ-Aminobutyric acid (GABA)-induced regional changes of extracellular Cl, K and Na concentration ([Cl] 0, [K] 0, [Na] 0), as well as of the extracellular space were measured with ion-sensitive microelectrodes in guinea pig hippocampal slices. Microdrop application of GABA to the pyramidal cell layer of CA3 or CA1 induced a decrease of [Cl] 0, while application to the dendritic layer of CA3 or CA1 induced an increase of [Cl] 0 in addition. All changes of [Cl] 0 persisted in the presence of TTX and were blocked by bath-applied bicuculline. The GABA-induced decrease of [Cl] 0 was reduced by bicuculline application to the pyramidal cell layer. The increase of [Cl] 0 was blocked by bicuculine application to the dendritic layer. Additionally, GABA induced an increase of [K] 0 and decreases/increases of [Na] 0. Changes of [Cl] 0, [K] 0, and [Na] 0 together were approximately electroneutral. [Cl] 0 increases were exaggerated and [Cl] 0 decreases partly masked by shrinkage of the extracellular space after GABA application. Changing [K] in the superfusate transiently changed GABA-induced [Cl] 0 movements in a way predicted from a change in driving force due to the effect of [K] on membrane potential. Then a partial recovery followed towards the original [Cl] 0 change. We conclude that inward and outward Cl transports maintain [Cl] i below equilibrium in CA3 and CA1 pyramidal somata and above equilibrium in CA3 and CA1 dendrites. The significance of ths Cl-distribution for hippocampal inhibition is discussed.