The acute effects of ethyl alcohol on mammalian central neurons were investigated using electrophysiological techniques and an in vitro model system, cultured fetal mouse spinal cord neurons. Intracellular recordings were made from the cultured neurons to evaluate the effect of alcohol (10-100 mM) on membrane potential, membrane permeability, amplitude of the action potential, sensitivity of the neurons to putative neurotransmitters and the process of synaptic transmission. Alcohol was applied by superfusion; putative amino acid neurotransmitters were applied by micropressure ejection. The most dramatic effect of alcohol on the spinal cord neurons was a reduction in the spontaneous activity (excitatory and inhibitory synaptic potentials and action potentials) and the glutamate evoked synaptic activity. Alcohol doses as low as 20-30 mM, concentrations which reflect blood levels during intoxication, were effective. Membrane potential, membrane permeability, and amplitude of the action potential were relatively resistant to these low doses of alcohol; at the higher alcohol doses, no effect or only modest alterations of these characteristics were observed. The responses of the neurons to the putative excitatory neuro-transmitter glutamate, and inhibitory transmitters GABA and glycine were also relatively resistant to alcohol exposure. These data indicate that acute exposure to alcohol has a predominantly inhibitory action on the activity of the cultured mammalian CNS neurons, and that this inhibition is most likely due to an alteration in the process of synaptic transmission.