The inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine directly cause an increase in conductance to Cl- by binding to ligand-operated ion channel receptors at the postsynaptic membranes, so that opening of Cl- channels usually leads to a net hyperpolarization. The GABA(A) receptor has separate but allosterically interacting binding sites for GABA, benzodiazepines, barbiturates, anesthetic steroids and the convulsant picrotoxinin. The GABA(C) receptor also forms a Cl- channel, however its pharmacology differs from that of the GABA(A) receptor. Neurotoxic organochlorine pesticides belonging to the group of polychlorocycloalkanes (cyclodienes and gamma-hexachlorocyclohexane or lindane) induce in mammals an hyperexcitability syndrome that can progress until the production of tonic-clonic convulsions. They act as non-competitive GABA antagonists interacting with the picrotoxinin site both in membranes and in intact cultured neurons, thereby inhibiting the GABA-induced Cl- flux following activation of either GABA(A) or GABA(C) receptors. We also report the effects of polychlorocycloalkanes on glycine-induced 36Cl- flux in primary neuronal cultures. The delta isomer of hexachlorocyclohexane is a depressant compound, that increases the GABA-induced Cl- flux and allosterically increases benzodiazepine binding at the GABA(A) receptor. We discuss the mechanism of action of these compounds in relation to the disruption of ligand-operated Cl- channel receptors and the relevance of their convulsant/depressant actions.