The role of brain corticotropin-releasing factor type 2 (CRF 2) receptors in behavioral stress responses remains controversial. Conflicting findings suggest pro-stress, anti-stress or no effects of impeding CRF 2 signaling. Previous studies have used antisauvagine-30 as a selective CRF 2 antagonist. The present study tested the hypotheses that 1) potential anxiolytic-like actions of intracerebroventricular (i.c.v.) administration of antisauvagine-30 also are present in mice lacking CRF 2 receptors and 2) potential anxiolytic-like effects of antisauvagine-30 are not shared by the more selective CRF 2 antagonist astressin 2-B. Cannulated, male CRF 2 receptor knockout ( n = 22) and wildtype littermate mice ( n = 21) backcrossed onto a C57BL/6J genetic background were tested in the marble burying, elevated plus-maze, and shock-induced freezing tests following pretreatment (i.c.v.) with vehicle, antisauvagine-30 or astressin 2-B. Antisauvagine-30 reduced shock-induced freezing equally in wildtype and CRF 2 knockout mice. In contrast, neither astressin 2-B nor CRF 2 genotype influenced shock-induced freezing. Neither CRF antagonist nor CRF 2 genotype influenced anxiety-like behavior in the plus-maze or marble burying tests. A literature review showed that the typical antisauvagine-30 concentration infused in previous intracranial studies (∼1 mM) was 3 orders greater than its IC 50 to block CRF 1-mediated cAMP responses and 4 orders greater than its binding constants ( K d , K i ) for CRF 1 receptors. Thus, increasing, previously used doses of antisauvagine-30 also exert non-CRF 2-mediated effects, perhaps via CRF 1. The results do not support the hypothesis that brain CRF 2 receptors tonically promote anxiogenic-like behavior. Utilization of CRF 2 antagonists, such as astressin 2-B, at doses that are more subtype-selective, can better clarify the significance of brain CRF 2 systems in stress-related behavior.