To establish whether radially determined lower esophageal sphincter pressure responds symmetrically or asymmetrically to anticholinergic medication, we compared the rightward and leftward pressure responses to intravenous atropine injection. In 12 normal adult volunteers, the decrease in highest leftward lower esophageal sphincter pressure with atropine was more marked (40% decrease) than rightward (20% decrease). The result of this differential response to atropine was to reduce right-left pressure asymmetry. Mean highest leftward pressure fell 15-30 min postinjection from 35 to 21 mmHg and mean highest rightward pressure fell from 22 to 18 mmHg. Studies of the pharmacologic effect of drugs on the human lower esophageal sphincter may give variable results depending on sampling orientation within the sphincter. These radial differences should be considered in interpreting the effect of drugs on the human lower esophageal sphincter.