The relationship between gastroesophageal reflux (GER) and asthma remains controversial. Asthma symptoms worsen with CER, 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 (EMC) signals were measured. Throat, swallowing, chest, and stomach discomfort and respiratory sensation were estimated with the Borg scale. Minute ventilation ((V) over dot E) 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. (V) over dot E was greater in the Bernstein-positive patients during AP. Tidal volume (Vr), Vrc, Vab, Pes, Pga, Es, and Edi did not change during AP. Chest discomfort (D) correlated with ventilation ((V) over dot E = 0.7 + 0.8 D; r = 0.67; p < 0.001) and respiratory effort sensation (B) (B = 0.2 + 0.4 (V) over dot E; r = 0.70; p < 0.001) during AP. AP did not inhibit diaphragm activity. Increased (V) over dot E may explain the paradox of CER worsening respiratory symptoms without changing lung function.