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Renal and hepatic levels of the rate-limiting gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were determined in control and intrauterine growth-retarded rate neonates and dams. Dexamethasone and surgically induced intrauterine growth retardation (IUGR) resulted in an elevation of neonatal renal PEPCK activity, but did not affect hepatic PEPCK levels. In the dam, glucocorticoid administration resulted in an increase in renal PEPCK, but did not affect the hepatic enzyme. We have demonstrated that, unlike the hepatic enzyme, renal PEPCK could potentially contribute to gluconeogenesis in utero, since dexamethasone administration significantly increased renal PEPCK at birth. This study confirms the hypothesis that hepatic and renal PEPCK activities are regulated independently in both the adult and neonatal animal.