Study objective: To study mechanisms of gastroesophageal reflux-induced bronchoconstriction during intraesophageal infusions. Design: Prospective study blinded to the subject. Setting: Outpatient pulmonary function laboratory at a 908-bed university hospital. Participants: Forty-seven adult subjects divided into four groups: asthmatics with reflux, 20; asthmatics, 7; gastroesophageal refluxers, 10; and normal controls, 10. Asthmatics were defined by American Thoracic Society criteria, and refluxers were defined by symptoms and 24-hour pH monitoring. Interventions: Dual antimony esophageal pH probe placed just below the upper esophageal sphincter and 5 cm above the lower esophageal sphincter. Intraesophageal infusions of normal saline solution followed by 0.1 N hydrochloric acid then normal saline solution were given for 15 to 18 min. Spirometry and specific airway resistance (SRaw) were performed after placement of pH probes, insertion of esophageal infusion tube, and after each infusion. Bernstein tests were assessed during esophageal infusions. Measurements and results: Peak expiratory flow rate (PEF) decreased with intraesophageal acid in all four groups (p<0.014). Esophageal acid clearance improved PEF in all groups except the asthmatics with reflux group that had a further decrease in PEF. These effects were not dependent on a positive Bernstein test or evidence of proximal reflux. The asthmatics with reflux group also had an increase in SRaw with intraesophageal acid, which continued to increase despite acid clearance. Conclusions: Intraesophageal acid infusions caused a decrease in PEF in all groups without evidence of microaspiration, implying a vagally mediated reflex may be involved. Esophageal mucosal inflammation, assessed by a positive Bernstein test, was not required. Asthmatics with reflux also had further decline in PEF despite acid clearance.