Gamma (gamma)-aminobutyric acid (GABA) acting via GABAA receptors is the brain's major inhibitory neurotransmitter system and exerts a crucial role in regulating brain excitability. A number of drugs interact with binding sites on GABAA receptors, and these include benzodiazepines, anticonvulsants, anaesthetics and neurosteroids (e.g. the progesterone metabolite pregnalone). GABAA receptors comprise five subunits (19 are known currently), and are classified into three major groups (alpha, beta and gamma) and several minor ones. The subunit make-up of a receptor, particularly its alpha-subunit content, determines its pharmacological characteristics. Thus, receptors that include an alpha1 subunit have a benzodiazepine (BZ) type I (BZ[I]) pharmacology and bind zolpidem and CL218,872 with high affinity, whilst receptors with alpha2, alpha3 or alpha5 subunits have a BZ type II (BZ[II]) pharmacology and bind these drugs with low affinity. In contrast to receptors that contain alpha4 and alpha6 subunits, which are diazepam-insensitive, both BZ(I) and -(II) bind diazepam and other benzodiazepines. The ligand selectivity of receptor subunits assists in their characterisation. Using immunochemical and ligand-binding techniques, the subunit composition of GABAA receptors has been shown to exhibit a degree of brain regional specificity. GABAA receptors are of great clinical significance in several disorders, including epilepsy, anxiety and alcoholism. In addition to treating epilepsy with drugs that target GABAA and BZ binding sites, epileptic lesions can be localised presurgically using radiolabelled BZ ligands. BZs are used commonly to treat anxiety, and studies suggest that BZ antagonists and inverse agonists (which induce the opposite effect to agonists at receptors) may be useful in alcohol rehabilitation.