Corticotropin-releasing hormone (CRH) is present in the adrenal gland acting as a paracrine factor via stimulation of the locally expressed CRH receptors. In this study, we examined if the adrenal CRH system also contains a key component of the neuronal CRH-containing system, the CRH-binding protein (CRH-BP). Our data show that: (i) the CRH-BP transcript is detectable using RT-PCR in total RNA isolated from rat adrenals, and (ii) its protein product is also found by western blot analysis in cell lysates. (iii) Immunohistochemical staining showed that adrenomedullary chromaffin cells produce the bulk of adrenal CRH-BP, an ability retained by the PC12 rat pheochromocytoma cell line. (iv) Regulation of adrenal CRH-BP expression by major modulators of the CRH system was also examined. Protein expression appears to be under the positive control of CRH itself, protein kinase A effector cAMP, glucocorticoids and interleukin (IL)-6. It is thus evident that CRH-BP may play a role in mediating their effects in the adrenal. (v) Differentiation of PC12 into neuron-like cells resulted in a significant increase in CRH-BP, parallel to the induction of the CRH peptide itself. In conclusion, CRH-BP mRNA and protein are present in normal rat adrenomedullary chromaffin cells and in the PC12 rat pheochromocytoma cell line, making the adrenal CRH system directly comparable with those described in the CNS.