The effect of the anaesthetic gas isoflurane was studied by intracellular recordings in neurones from rat hippocampal cortex and neurones from human neocortex in vitro. Anaesthetic concentrations of isoflurane abolished spontaneous activity and reduced synaptically evoked activity without rendering individual cells inexcitable or preventing evoked synaptic activity to increased afferent input. Induced epileptiform activity was not observed. Isoflurane reversibly hyperpolarized the cell membrane in a dose-dependent manner, isoflurane 1.5, 3 and 5% causing 4 +/- 1, 6 +/- 2 and 8 +/- 2 mV (mean +/- SD) hyperpolarization, respectively. The hyperpolarization was accompanied by a reduction in the input resistance, 18 +/- 3% for 3% isoflurane. The effects remained unchanged after synaptic transmission was blocked. Five experiments with intracellular recordings from human cortical neurones in vitro showed identical results.