The orbitofrontal cortex (OFC) plays a fundamental role in motivated behavior and decision-making. In humans, OFC structure and function is significantly disrupted in drug using and dependent individuals, including those exhibiting chronic alcohol use and alcoholism. In animal models, the OFC has been shown to significantly influence the seeking of non-alcohol drugs of abuse. However direct investigations of the OFC during alcohol seeking and use have been more limited. In the studies reported here, we inactivated lateral (lOFC) or medial OFC (mOFC) subregions in rats during multiple stages of alcohol seeking. After one month of intermittent access to homecage 20% ethanol (EtOH), rats were trained to self-administer EtOH under an FR3 schedule and implanted with cannulae directed to lOFC or mOFC. We inactivated OFC subregions with baclofen/muscimol during EtOH self-administration, extinction, cue-induced reinstatement, and progressive ratio testing to broadly characterize the influence of these subregions on alcohol seeking. There were no significant effects of mOFC or lOFC inactivation during FR3 self-administration, extinction, or progressive ratio self-administration. However, lOFC, and not mOFC, inactivation significantly decreased cue-induced reinstatement of EtOH seeking. These findings contribute new information to the specific impact of OFC manipulation on operant alcohol seeking, support previous studies investigating the role of OFC in seeking and consumption of alcohol and other drugs of abuse, and indicate a specific role for lOFC vs. mOFC in reinstatement.Copyright © 2020 Elsevier Ltd. All rights reserved.