School of Medicine, Philadelphia, PA 19104, USA y-Aminobutyric acid (GABA) was discovered over 40 years ago in brain [l-3], where it was later identified as the key inhibitory neurotransmitter [4, 5]. Since that time, evidence has accumulated that this amino acid may be of functional importance not only in the central nervous system but also in peripheral tissues, such as gut, urinary bladder, heart, lung, ovary and pancreas [6-91. The concentration of GABA in mammalian organs varies considerably; it is particularly high in brain, with an average value of 2-3 pmol/g wet weight (20-30 pmol/g protein) and a regional distribution of 10-30 pmol/g protein [lo, 111. By contrast, in most peripheral tissues GABA content is low, about 1% of that in brain [6-91. An exception is the female genital tract [12, 13] and pancreatic islets [14, 15] where considerably larger amounts have been found. Several recent reviews have evaluated the possible role of GABA outside the mammalian brain [16-20], but none dealt specifically with its metabolism and physiological function in either the pancreas or the islets of Langerhans. The object of this article is to correct this oversight and to provide a critical review of the literature on the subject, to identify areas of obscurity and/or controversy, and to suggest directions for future investigations.