Wake-promoting effects of orexins and corticotropin-releasing hormone (CRH) are well documented. Neuronal interactions between these two systems and anatomical data point to a reciprocal influence of these neuropeptides. We examined in how far an impaired CRH system may influence the circadian rhythm of extracellular orexin levels in mice. The basal levels of orexin were collected unilaterally from the lateral hypothalamus over 24 h in conditional CNS-specific CRH receptor type 1 (CRH-R1) knockout animals and control littermates. No significant differences were obtained between both groups suggesting that under basal conditions the circadian variation of hypothalamic orexin is not mediated by CRH, at least not via CRH-R1.