Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects.