Our laboratory has previously shown that systemically administered ethanol inhibits NMDA-evoked electrophysiological activity in some, but not all, neurons in the medial septum. In the present report, it was found that ethanol, when applied locally via electro-osmosis, potently inhibited NMDA-evoked neuronal activity in a current-dependent manner in the inferior colliculus and hippocampus. In contrast, locally applied ethanol failed to inhibit NMDA-evoked activity in the lateral septum. The inhibition by ethanol of NMDA-evoked activity in the inferior colliculus was specific, in that ethanol failed to inhibit neuronal activity of the inferior colliculus evoked by the excitatory neurotransmitter glutamate. These findings indicate that ethanol can specifically inhibit NMDA-evoked activity in vivo via a local action, and that the ability of ethanol to inhibit NMDA-evoked activity varies regionally in brain. The possibility that these results are explained by the existence of two types of NMDA receptors, one sensitive to ethanol, the other insensitive to ethanol, is discussed.