The possibility that conformational changes of glutamate dehydrogenase represent a way of controlling insulin release was evaluated by measuring the levels of α-ketoglutarate and glutamate in β-cells in different states of functional activity. The α-ketoglutarate content corresponded to about 0.5 mmoles per kg dry weight. There was a 16% reduction when the β-cells were stimulated with carbutamide, whereas no significant changes occurred in the presence of high glucose concentrations or glibenclamide. The β-cell content of glutamate corresponded to 20-26 mmoles per kg dry weight. Neither stimulation of insulin release by sulfonylureas or glucose nor inhibition of this process by diazoxide affected the level of the latter metabolite. 1 Supported by grants from the United States Public Health Service (AM-12535), Swedish Medical Research Council (12x-562), Swedish Diabetes Association andthe Medical Faculty of Umea. For generous supplies of material we are indebted to Farbwerke Hoechst AG, Frankfurt/M, Germany (carbutamide and glibenclamide), AB Kabi, Stockholm, Sweden (serum albumin) and Schering Corporation, Bloomfield, N.J. (diazoxide).