CRH occurs in the adrenal medulla of rats. We were interested to know whether CRH affects meduallary chromaffin cells in the absence of ACTH. We investigated the morphological changes of the adrenal medulla in Sprague Dawley rats with light and electron microscopy in normal rats, hypophysectomized rats, and hypophysectomized rats following injections of CRH (10 micrograms = 3 nmol for three days). Chromaffin cells were characterized by immunohistochemistry (anti-tyrosine hydroxylase). At light microscopy level chromaffin cells of hypophysectomized rats were reduced in number. On electron microscopy the number of granules and cell organelles were decreased. Following injections of CRH the medulla regained a more compact texture with cell organelles homogenously distributed, but with chromaffin granules still being reduced in number. Immunohistochemistry allowed the identification of chromaffin cells located within the adrenal cortex. In hypophysectomized rats these cells showed fewer signs of alterations compared to cells located within the medulla itself and had recovered better after treatment with CRH. In conclusion, CRH seems to exert a trophic effect on chromaffin cells in the absence of pituitary ACTH. This observation may provide further evidence for a close interaction of the two neuroendocrine stress systems.