Food restriction is known to ameliorate many of the adverse physiologic effects of age. In this study, we have examined the effect of food restriction on the induction of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) in liver and kidney following a 12-h fasting period in young (6 month) and old (24 month) ad libitum-fed and food-restricted male Fischer 344 rats. In the liver, following the 12-h fast, the activity of PEPCK increased approximately 2-fold in the young ad libitum fed rats and 3-fold in the young restricted animals. However, PEPCK activity remained unchanged in response to the 12-h fast in the 24 month old ad libitum fed rats. In the old restricted rats, the induction of PEPCK mimicked that of the young rats (PEPCK activity increased 2-fold within the 12-h fasting period). Therefore, dietary restriction not only enhanced the induction response in the liver in young rats, but also restored the induction of hepatic PEPCK in the old animals. In the kidney, there was no effect of age or dietary restriction on the induction of PEPCK as the activity of renal PEPCK did not change in response to the 12-h fast in any of the four groups of rats.