BACKGROUND: Prostaglandins inhibit the contraction of gastrointestinal smooth muscle and may decrease lower esophageal sphincter tone. The purpose of this study was to determine whether the cyclooxygenase-2 inhibitor celecoxib (Celebrex) could increase lower esophageal pressure (without affecting gastric emptying) compared to placebo and cisapride (Prepulsid), a compound previously used to treat reflux disease. MATERIALS AND METHODS: Six mongrel dogs were assigned to receive celecoxib, cisapride, and placebo using a randomized cross-over design with a 1-week washout period between treatments. Prior to dosing, each dog underwent an esophagopexy to provide access to the esophagus and stomach. On the fourth day of dosing, sphincter tone was measured in awake unsedated dogs using radial manometry. In a different set of six dogs, liquid and solid gastric emptying rates were scintigraphically determined. RESULTS: Celecoxib significantly increased mean and average maximum lower esophageal pressures compared to placebo without affecting the gastric emptying rate. The magnitudes of these increases were similar to that produced by cisapride. CONCLUSIONS: Celecoxib had a positive effect on canine lower esophageal sphincter tone. This finding, combined with the drug's low incidence of gastrointestinal toxicity, suggests that celecoxib may warrant consideration and investigation as a pharmacotherapy for human reflux disease.