Recent evidence has shown that abnormal signal transduction is related to non-pathological memory impairment among aged subjects. Members of the CREB family of transcription factors contain enhancers (i.e., CREB1) and repressors (i.e., CREB2) of transcription and interact with numerous signaling proteins to mediate the transition from short-term to long-term memory. In this study, quantitative Western blotting was used to determine the levels of CREB1 and CREB2 in homogenates from hippocampi of individual 6- and 24-month-old male Long-Evans rats trained first on a place-learning task in the Morris water maze, then on a transfer task. Based on spatial memory performance, aged rats were characterized into two groups; aged-unimpaired rats (AU) had scores within the range of the young (Y) and aged-impaired rats (AI) fell outside of that range. Overall, CREB1 protein was significantly lower in aged rats in comparison with young rats. Aposteriori analysis showed that this difference was due to a significant decrease in CREB1 levels among aged-impaired rats, whereas aged-unimpaired rats had CREB1 levels comparable to young rats. There was no significant change in levels of CREB2 protein between young and aged rats. These results show that the dysregulation of CREB1 protein may contribute to the spatial memory deficits observed among some aged subjects.