BackgroundLarge conductance, calcium‐ and voltage‐activated potassium (BK) channels regulate neuronal excitability and neurotransmission. They can be directly activated by ethanol (EtOH) and they may be implicated in EtOH dependence. In this study, we sought to determine the influence of the auxiliaryβ1 andβ4 subunits on EtOH metabolism, acute sensitivity to EtOH intoxication, acute functional tolerance, chronic tolerance, and handling‐induced convulsions during withdrawal.MethodsMotor coordination, righting reflex, and body temperature were evaluated inBKβ1 andβ4 knockout, heterozygous, and wild‐type mice following acute EtOH administration. Chronic tolerance and physical dependence were induced by chronic intermittent inhalation of EtOH vapor.ResultsConstitutive deficiency inBKβ1 orβ4 subunits did not alter the clearance rate of EtOH, acute sensitivity to EtOH‐induced ataxia, sedation, and hypothermia, nor acute functional tolerance to ataxia.BKβ1 deletion reduced chronic tolerance to sedation and abolished chronic tolerance to hypothermia, whileBKβ4 deletion did not affect these adaptations to chronic EtOH exposure. Finally, the absence ofBKβ1 accelerated the appearance, while the absence ofBKβ4 delayed the resolution, of the hyperexcitable state associated with EtOH withdrawal.ConclusionsAltogether, the present findings reveal the critical role ofBKβ1 in behavioral adaptations to prolonged, repeated EtOH intoxication.