Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension.(ABSTRACT TRUNCATED AT 250 WORDS)