Corticotropin-releasing factor (CRF) is a key mediator of the behavioral, autonomic, and endocrine responses to stress. CRF binds two receptors and a CRF-binding protein (CRF-BP), which may inactivate or modulate the actions of CRF at its receptors. The amygdala is an important anatomical substrate for CRF and contains CRF, its receptors, and CRF-BP. Few studies have examined the effects of acute stress on the regulation of amygdala CRF-BP with other CRF system genes. Therefore, we examined the time course of the effects of acute restraint stress on central (CeA) and basolateral (BLA) amygdala CRF system genes. Consistent with our previous study, acute stress increased BLA CRF-BP mRNA shortly after stress offset. Surprisingly, BLA CRF-BP mRNA remained elevated up to 21 h after the stressor. This effect was selective in the BLA as stress did not alter CeA CRF-BP mRNA, and there were no changes in CRF or CRF receptor mRNAs in either amygdala nucleus. These results suggest that alterations in BLA CRF-BP gene expression are a primary response of the BLA/CeA CRF system to acute stress. Because CRF-BP can modulate CRF action, changes in amygdala CRF-BP levels after stress exposure may affect the ability of an organism to adapt to future stressors.