Ethanol (ETH) and general anesthetics have been reported to facilitate the chloride channel opening, possibly, or at least partly, through an interaction with the GABA-benzodiazepine (BZ) receptor-gated chloride ionophore "supramolecular complex". Recently Ro 15-4513, a novel BZ ligand, has been indicated as a potent and selective antagonist of various ETH-induced behavioral and biochemical effects. However, since its precise characterization is still a matter of debate, we have tested and compared the effect of Ro 15-4513, as well as its antagonism against ETH, in two objective electrophysiological parameters, i.e., the electroencephalograph (EEG) pattern in freely moving rats and single unit activity of reticulata neurons. Ro 15-4513 produced an EEG state of alertness and antagonized the behavioral impairment and the EEG deterioration by ETH. However, while its protective action was consistent against moderate doses (2 g/kg) of ETH, it was much less evident versus higher doses (4 and 8 g/kg). On reticulata cells, Ro 15-4513 potently stimulated their spontaneous firing and reversed the depression by both ETH and Na-pentobarbital. Moreover, the beta-carboline DMCM also had similar effects. The "pure" BZ antagonist Ro 15-1788 was completely inefective against ETH, yet fully cancelled the reversing actions of Ro 15-4513 and DMCM upon ETH or Na-pentobarbital effects. It is concluded that Ro 15-4513 behaves as a BZ inverse agonist, so that its opposition to ETH and Na-pentobarbital is probably the result of its "negative" coupling with the BZ recognition site that triggers the closing of chloride channels. It suggests that BZ inverse agonists might constitute, in the near future, a new class of analeptic drugs.