The molecular mechanism whereby GABA system is modified by benzodiazepines (BDZs) was studied in vivo and in vitro. In vivo BDZ like the GABA mimetic, muscimol antoagonize the isoniazid-induced convulsions, and the isoniazid-induced increase of cerebellar cGMP and pituitary cAMP content. In vitro BDZs facilitate binding of GABA to its receptor sites by competing with the endogenous membrane protein which acts as an inhibitor of high affinity Na+-independent GABA binding to synaptic membrane preparations. The same endogenous inhibitor of GABA binding competes with BDZs for their specific sites. This increase in the binding affinity of GABA for its postsynaptic site may represent the molecular mechanism by which BDZs facilitate GABA transmission in vivo. These observations may help in elucidating details of the supramolecular nature of postsynaptic GABA and BDZs receptors and also may offer a simple means for studies of the biochemical defects in anxiety states.