We have presented several lines of circumstantial evidence suggesting a possible role for CRH in the panic disorder syndrome. Such a role has by no means been demonstrated and is indeed challenged by several lines of contradictory data. Critical evaluation of this hypothesis must await further basic research on the role of hypothalamic and extrahypothalamic CRH in stress-mediated phenomena and on their interrelationships. Moreover, additional clinical research will be required to further delineate the landscape of hypothalamic-pituitary-adrenal function in patients with panic disorder both during acute panic episodes and intercurrently.