Transfer to seawater (SW) in rainbow trout elicits an increase in plasma cortisol and a bout of anorexia. Although the corticotropin-releasing factor (CRF) system has known hypophysiotropic and anorexigenic properties, it is not known whether CRF-related peptides originating from either the forebrain or the caudal neurosecretory system (CNSS) play a role during SW acclimation. Therefore, we examined the effects of SW transfer on food intake, plasma osmolality, hypothalamic-pituitary-interrenal axis activity, and on the expression of CRF and urotensin I (UI) in the forebrain and the CNSS. While SW transfer chronically suppressed food intake over a 2-week period, it transiently increased plasma osmolality, ACTH, and cortisol. Similarly, 24-h after SW transfer, hypothalamic and preoptic area CRF mRNA levels were significantly increased but recovered to pre-transfer levels within 7 days. Conversely, SW transfer elicited a delayed increase in hypothalamic UI mRNA levels and had no effect on preoptic area UI expression. In the CNSS, SW exposure was associated with parallel increases in CRF and UI mRNA levels from 24 h post transfer through 7 days. Finally, in situ hybridization demonstrated an extensive and overlapping pattern of CNSS CRF and UI expression. These results differentially implicate specific neuronal populations of the CRF system in the acute and chronic responses to a hyper-osmotic stress and suggest that forebrain and CNSS CRF-related peptides have different roles in the coordinated response to fluid balance disturbances.