In healthy subjects, the rate of acid reflux during transient lower esophageal sphincter relaxations (TLESRs) is more frequent at the proximal margin of the LES. In this study, we investigated the hypothesis that the rate of acid reflux at the proximal margin of LES during TLESRs is similar in reflux disease to that in healthy subjects. Concurrent esophageal manometry and pH monitoring were performed in the sitting position for 3 hr after a standard meal in 10 patients with reflux disease and 10 age-matched healthy controls. The rate of TLESRs in patients with reflux disease (5.0/hr [3.3-6.7]; median [interquartile range]) was similar to that of controls (4.5/hr [3.7-5.7]). The incidence of acid reflux 7 cm above the LES during TLESRs in patients (48.1% [27.2-71.4%]) was significantly higher than that in controls (10.9% [0.0-18.8%]) but there was no difference 2 cm above the LES (75.0 [69.2-87.5] vs. 74.3 [55.5-90.0%]). The rate of TLESRs and the incidence of acid reflux during TLESRs are not increased in reflux disease. These findings, therefore, indicate that reflux disease is not a disorder of TLESRs and relates more to the proximal extent of the refluxate.