Membrane hyperpolarization (increase in resting potential) together with a conductance increase has been suggested as a common mechanism of anesthetic action. The current study compared the effects of halothane, enflurane, and isoflurane on resting membrane potential and conductance of hippocampal CA1 neurons in vitro. At 1 MAC, halothane produced significant (P less than 0.01) hyperpolarization (-2.8 +/- 1.3 mV, mean +/- SD) accompanied by a conductance increase (6.2 +/- 2.7%). Enflurane also produced a significant (P less than 0.001) hyperpolarization (-3.15 +/- 1.2 mV); however, this was accompanied by a conductance decrease (-4.5 +/- 1.5%). Isoflurane produced variable effects. Anesthetic-induced hyperpolarization was maximal in neurons with more negative initial resting potentials and was reduced by depolarization. Across agents, these relatively small changes in resting potential were not correlated with decreases in excitability as measured by synaptically evoked population spike depression. The results are not consistent with a common action of the three agents on a single ionic channel.