This study is focused to learn about the cellular localization of transcription factors binding to the cAMP response element-CREBs-in the brain of normal rats and in animals subjected to excitotoxic cell damage. For this purpose, CREB-1 and CREB-2 immunoreactivity is examined in the developing and adult rat brain under physiological conditions, and following systemic kainic acid (KA) injection at convulsant doses in the adult, as a validated experimental model of excitotoxic injury. CREB-1 immunoreactivity is constitutively expressed in periventricular glia and Bergmann glia, and appears in reactive astrocytes following KA-induced excitotoxic cell damage. In contrast, CREB-2 is constitutively expressed in all neurons of the cerebrum, cerebellum and brain stem in the developing and adult brain. CREB-2 immunoreactivity is not increased following KA excitotoxic cell damage. These results demonstrate that CREB-1 and CREB-2 in the brain of the rat are localized in separate cellular compartments and that their expression is differentially regulated in pathologic states.