The benzodiazepine--gamma-aminobutyric acid (GABA) receptor--ionophore system is an oligomeric complex, composed of at least three interacting components. These three components have been well characterized in vitro by radioreceptor binding assays. A variety of centrally acting anxiolytic, depressant, anticonvulsant and convulsant drugs, which affect GABAergic transmission, bind to one of the sites and modulate the binding of ligands at the other sites. Thus, depressant barbiturates, nonbarbiturate hypnotics (like etomidate) and pyrazolopyridines (like etazolate), while inhibiting the binding of alpha-dihydropicrotoxinin (DHP), enhance the binding of GABA and benzodiazepines. These enhancing effects are blocked by convulsant drugs that inhibit the binding of dihydropicrotoxinin and also by bicuculline. These interactions involving barbiturates and other modulatory drugs, exhibit stereoselectivity, anion dependence and brain regional selectivity. Several classes of drugs which facilitate GABAergic transmission appear to interact with the sites for GABA and benzodiazepines allosterically via the dihydropicrotoxinin site of the oligomeric complex. The GABA system has also been implicated in a variety of pathological conditions, including anxiety, seizure activity, movement disorders, cardiovascular control, pain and in drug dependence. Since most of the GABA agonists do not pass the blood-brain barrier, future trends in the pharmacology of GABA may be the development of drugs that will activate the GABA receptor system via picrotoxinin or benzodiazepine sites.