The effects of parathyroid hormone, adenosine 3' : 5'-monophosphate (Ado-3' : 5'-P) and oleate on renal metabolism have been studied in isolatcd kidney-cortex tubules from starved rats. Substrate uptake and glucose formation have been determined with L-lactate, pyruvate, glutamate, and glycerol as substrates.The results indicate that parathyroid hormone and A d o 3 : 5'-P increase renal gluconeogenesis by the same mechanism, which however, differs from the effects brough about by free fatty acids :1. Parathyroid hormone and Ado-3' : 5'-P increased glucose formation from L-lactate, pyruvate and glutamate. The stimulatory effect of parathyroid hormone was always smaller compared with thitt of Ado-3' :5'-P. Glucose formation from L-lactate was shown to be stimulated with hormone doses as low as 1 -10 nM. Oleate had an increasing effect on glucose formation from L-lactate and glycerol, but no effect on glucose formation from 10 mM pyruvate and inhibited gluconeogenesis from glutamate.2 . The stimulatory action of parathyroid hormone and Ado-3' : 5'-P was accompanied by an increase in substrate uptake, whereas oleate decreased substrate uptake.3. The effects of parathyroid hormone and Ado-3' : 5'-P on kidney-tubule metabolism were not additive, when both substances were added together.4. All effects of oleate were found to be unchanged in the presence of parathyroid hormone and Ado-3' : 5'-P or both.The results suggest two different mechanisms which may regulate renal gluconeogenesis additively .Renal gluconeogenesis has been studied in isolated perfused kidney [1,2], kidney-cortex slices [3,4] and more recently in isolated kidney tubules [5,6]. Among other metabolic pathways lipid and carbohydrate metabolism have been studied most extensively in the past 20 years. Fatty acid oxidation has been shown to be the main metabolic fuel [4,7] whereas carbohydrates were found to be oxidized to only a very small extent. In the presence of appropriate substrates gluconeogenesis could be observed a t appreciable rates which, related to tissue wet weight, may exceed those found in liver [8,9]. These results conform with the higher activities of all gluconeogenic enzymes found in the kidney [lo].