The relationship between gastroesophageal reflux (GER) and asthma remains controversial. Asthma symptoms worsen with GER, but are not consistently related to changes in lung function. The purpose of this study was to determine whether acid perfusion (AP) of the esophagus alters ventilation and causes respiratory symptoms. Nonasthmatic patients with normal lung function and esophageal disease (16 females and nine males, FEV1 %predicted = 99+/-9.6), underwent a Bernstein test after motility testing. Airflow, rib cage (Vrc), and abdominal (Vab) tidal volumes, esophageal (Pes) and gastric (Pga) pressure, and surface (Es) and esophageal (Edi) diaphragm electromyographic (EMG) signals were measured. Throat, swallowing, chest, and stomach discomfort and respiratory sensation were estimated with the Borg scale. Minute ventilation (VE) increased during AP and declined during recovery with saline perfusion of the esophagus (7.1+/-1.5 to 8.5+/-2.4 to 7.3+/-2.1 L/min; n = 25; p = 0.0002). Respiratory rate (RR) went from 13.6+/-2.6 to 15.8+/-3.4 to 15.3+/-3.1 breaths/min (n = 25; p = 0.0002) during AP. VE was greater in the Bernstein-positive patients during AP. Tidal volume (VT), Vrc, Vab, Pes, Pga, Es, and Edi did not change during AP. Chest discomfort (D) correlated with ventilation (VE = 0.7 + 0.8 D; r = 0.67; p < 0.001) and respiratory effort sensation (B) (B = 0.2 + 0.4 VE; r = 0.70; p < 0.001) during AP. AP did not inhibit diaphragm activity. Increased VE may explain the paradox of GER worsening respiratory symptoms without changing lung function.