The characterization of corticotropin-releasing factor (CRF) and CRF receptors and the use of specific CRF antagonists have paved the way to establish a key role of brain CRF in the coding of the stress response. CRF injected into the cerebrospinal fluid or the periphery inhibits gastric emptying in various species. The paraventricular nucleus of the hypothalamus and dorsal vagal complex are brain sites of action for CRF. Endogenous brain CRF plays a role in mediating psychological, physical, somatovisceral, and immunological stress-induced delayed gastric emptying in rats. Postoperative gastric ileus is also prevented by peripheral injection of CRF antagonists. Cyclic vomiting syndrome (CVS) is precipitated by stimuli or states associated with stimulation of CRF release, and the resulting endocrine, autonomic, and visceral changes are indicative of central CRF activation. Moreover, empiric pharmacotherapy alleviating CVS symptoms are known experimentally to block CRF release or action. The relevance of central CRF activation in the pathophysiology of CVS deserves further consideration.