We utilized biochemical and electrophysiological methods to compare the effects of anesthetic and anticonvulsant barbiturates on gamma-aminobutyric acid (GABA) receptor-coupled responses. Biochemical analysis involved barbiturate regulation of the affinity of a radiolabeled benzodiazepine for benzodiazepine receptors. The electrophysiological method involved regulation of somatic recurrent inhibition of CA1 pyramidal cells in the hippocampal slice preparation. We found that anesthetic (secobarbital and pentobarbital) but not anticonvulsant (phenobarbital and diphenylbarbituric acid) barbiturates significantly enhanced GABA receptor-coupled responses in both the biochemical and electrophysiological preparations. The results indicate that the anticonvulsant actions of barbiturates may not depend on their ability to enhance GABAergic neuronal activity.