Dehydration induces Fos expression and increases the length of the vasopressin (VP) mRNA poly-A tail and the content of VP mRNA in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus. The current studies were performed to evaluate the effect of aging on these responses. Fischer 344 rats of 4, 14, and 28-30 months of age were either water deprived for 72 h or allowed ad libitum access to water. Fos induction in the SON and PVN was examined by immunocytochemistry in order to provide an index of cellular activation. VP mRNA content and size was examined in SON by Northern analysis as an index of VP synthetic capacity. Dehydration induced the expected increase in plasma osmolality in all three ages, however, serum VP was only increased in the 4- and 14-month-old rats. The increase in serum VP was accompanied by a decrease in VP content of the posterior pituitary (PP) in the dehydrated 4- and 14-month-old rats. PP VP content was reduced in both the hydrated and dehydrated old rats relative to the other ages (P = 0.0007). Fos was induced in both SON and PVN of all water deprived rats regardless of age. The density of Fos staining was increased in both nuclei following dehydration (SON, P = 0.002; PVN, P = 0.0001). There was also a significant increase in the number of cells expressing Fos in both nuclei in the dehydrated animals (SON, P = 0.002; PVN, P = 0.0056). There was no significant effect of age on the density of Fos staining. In contrast, dehydration failed to elicit the expected increase in VP mRNA size and content in the SON of the aged dehydrated rats although both of these parameters were increased in the 4- and 14-month-old rats (P < 0.05). Thus, the inability of old Fischer rats to increase serum VP during chronic dehydration is not caused by decreased activation of the neurons (as indicated by Fos induction), but apparently reflects depletion of PP stores of VP due to an inability to increase the amount of VP mRNA available for translation.