Stress has been reported to influence ethanol consumption and relapse in abstinent alcoholics. The present study examined if prolonged alterations in neurophysiological responses to corticotropin-releasing factor (CRF) and neuropeptide Y (NPY), peptides known to influence stress responses, would persist during protracted ethanol abstinence. Male Wistar rats were chronically exposed to ethanol vapour (EtOH group) or air (control group) for 6 weeks. Upon removal from the vapour chambers, recording electrodes were implanted in the cortex and amygdala. The effects of intracerebroventricular infusions of CRF and NPY on electroencephalogram (EEG) and event-related potentials (ERPs) were then assessed 10-15 weeks after withdrawal from ethanol. Following abstinence from ethanol, the EtOH group displayed increased power in the 6-8 Hz frequency range and increased stability in the cortical EEG. In addition, in the EtOH group the amplitude of the P2 ERP component in the frontal cortex was decreased and the latency of the P3 ERP component in the parietal cortex was delayed, compared to the control group during baseline recording conditions. The EtOH group was also more responsive to CRF and NPY. CRF significantly increased cortical power (6-8 Hz) and increased cortical EEG stability in the EtOH group, compared to controls. Additionally, NPY significantly decreased the amplitude of the N1 ERP component in the amygdala of the EtOH group, but not in the control group. This enhanced sensitivity to CRF and NPY following chronic ethanol exposure and abstinence suggests that these peptidergic systems may play a role in the symptomatology of the prolonged abstinence syndrome.