Although corticotropin-releasing factor (CRF) is thought to act as a neurotransmitter to activate the locus coeruleus (LC) during hypotensive stress, the consequences of LC activation by CRF are unknown. In the present study a hypotensive challenge that activated rat LC neurons also produced cortical electroencephalographic (EEG) correlates of arousal. Selective, bilateral LC inactivation by local clonidine infusion prevented EEG activation associated with hypotension. Additionally, bilateral LC infusion of CRF antagonists prevented both LC and EEG activation by this challenge. These results indicate that CRF, acting as a neurotransmitter to activate LC during stress, has a powerful of modulatory influence over global forebrain electrophysiological activity.