The effect of trimoprostil, and oral trimethyldesoxy prostaglandin E2 analog with antisecretory and cytoprotective activity, on esophageal motility was evaluated in a double-blind, three-way crossover study. Using antisecretory and cytoprotective single oral doses, 0.75 and 1.5 mg of trimprostil was compared with placebo in 12 healthy male volunteers. Motility parameters measured included lower esophageal sphincter pressure, amplitude, velocity, and duration of esophageal contractions. Unlike most previously reported prostaglandin E2 infusion studies, our study demonstrated that oral trimoprostil at low or high doses, when compared with placebo, had no effect on lower esophageal sphincter pressure or distal esophageal peristaltic amplitude in response to wet swallows. Therefore, oral administration of methylated prostaglandin E2 analogs would not be expected to contribute to esophageal reflux.