1. In addition to binding to GABAA receptors in the central nervous system, benzodiazepines have also been reported to recognize high affinity binding sites in several different peripheral tissues. 2. These peripheral benzodiazepine receptors likely consist of distinct integral membrane proteins, which are predominantly localized in the outer mitochondrial membrane and may be associated to form a heteropolymeric receptor complex. One such protein, identified for its ability to bind a class of benzodiazepines and isoquinolines, has been purified and the corresponding complementary DNA (cDNA) has been cloned and characterized. Furthermore, the structure of the rat gene encoding this protein has been clarified, thus potentially opening new insights into the molecular mechanisms responsible for receptor regulation. 3. Although the exact physiologic and/or pharmacologic role of peripheral benzodiazepine receptors is still unknown, their wide tissue distribution suggests an involvement in many cellular phenomena. 4. In particular, several lines of investigation indicate that these receptors, densely expressed on airway smooth muscle of various species, may contribute to the modulation of bronchomotor tone and perhaps to the pathogenesis of asthma and airway hyperresponsiveness.