Historical accounts of alcohol administration to patients with breathing problems suggest that alcohol may have bronchodilating properties. We hypothesized that acute alcohol exposure will alter airway responsiveness (AR) in mice. To test this hypothesis, C57BL/6 mice were fed either 20% alcohol in drinking water (fed) or received a single intraperitoneal (ip) injection of alcohol (3 g/kg). Control groups received regular drinking water or ip saline. AR was assessed by means of ventilation or barometric plethysmography and reported as either total lung resistance or enhanced pause for each group of mice. To confirm alcohol exposure, elevated blood alcohol levels were documented. Alcohol feeding significantly blocked methacholine-triggered AR compared with water-fed controls. Comparable blunting of AR was also accomplished through a single ip injection of alcohol when compared with saline-injected controls. The alcohol response was slowly reversible in both routes of administration after withdrawal of alcohol: AR attenuation by alcohol persisted 12-20 h (ip) or up to 2 wk (fed) after blood alcohol cleared consistent with a sustained bronchodilator effect. These data demonstrate that brief alcohol exposure blunts AR in this murine model of alcohol exposure suggesting a role for alcohol in the modulation of bronchial motor tone.