Intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) peptide fragments with low affinity for CRF receptors reportedly improves cognitive performance without producing anxiety. These compounds are hypothesized to act by displacing endogenous peptide from the CRF-binding protein (CRF-BP). To test this hypothesis, the present study determined whether the performance-enhancing potency of CRF fragments was related to their affinity for the CRF-BP. Rank ordering of the optimal doses of these compounds for facilitating spatial navigation corresponded to their affinity for the CRF-BP. i.c.v. pretreatment with performance-enhancing doses of r/h CRF(1-41)-OH (5 micrograms) or r/h CRF(6-33) (25 micrograms) did not increase emotionality. These findings replicate the dissociability of the cognition- and anxiety-related effects of CRF-related compounds and suggest that CRF fragments facilitate performance via the CRF-BP.