Renal as well as hepatic gluconeogenesis is inappropriately accelerated in the diabetic state when plasma glucose levels are elevated. Known regulatory mechanisms influence gluconeogenesis in both organs. However, under certain circumstances gluconeogenesis may be affected in one organ and not the other. Recent studies with the tryptophan metabolite, quinolinate, suggest that hepatic gluconeogenesis in the diabetic is unaffected by this agent, whereas gluconeogenesis is blocked in the normal liver. These experiments have been interpreted as providing evidence for the lack of a specific physiologic repressor for gluconeogenesis in diabetic liver. In the present study quinolinate and hydrazine are shown to be effective inhibitors of the accelerated gluconeogenesis in the renal cortex of diabetic rats. Thus, the renal gluconeogenic mechanism in diabetics retains the capacity to recognize quinolinate as an inhibitor, but may be influenced by the depressed conversion of tryptophan to quinolinate in the intact diabetic organism.