The nucleotide sequence CTGTGCGCGCAG is a core corticotropin-releasing hormone (CRH) responsive element in the proopiomelanocortin (POMC) promoter that gives 5-7 fold stimulation of POMC transcription by CRH. This region binds a novel transacting factor, proopiomelanocortin corticotropin-releasing hormone responsive element binding protein 1 (PCRH-REB-1), recently cloned from CRH-stimulated pituitary cells. We conducted in situ hybridization histochemistry experiments, using a species-specific, antisense, 35S-labeled PCRH-REB-1 riboprobe, to determine the pattern of PCRH-REB-1 gene expression in the brain, and showed that PCRH-REB-1 mRNA is localized not only in pituitary, but it is also found in discrete brain regions such as septal nuclei, hypothalamus, cortex, hippocampus, amygdala, and cerebellum. Those regions contain CRH or CRH receptors, and respond to CRH. We hypothesize that PCRH-REB-1 may be a marker of cellular responsiveness to CRH in the brain and pituitary, and might therefore be useful in the evaluation of CRH function and in the identification of clinically effective CRH agonists and antagonists.