BACKGROUND Trimebutine is an opiate modulator of the gastrointestinal motility that interacts with enkephalinergic receptors. OBJECTIVE To evaluate the effects of trimebutine (50 mg intravenous injection) on the motility of the sphincter of Oddi (SO) as assessed by endoscopic manometry. METHODS Endoscopic manometry was performed on 15 cholecystectomized patients who presented with symptoms suggestive of SO dysfunction. Prior to the endoscopic manometry, endoscopic ultrasonography was performed in order to rule out the possible presence of a bile duct stone. RESULTS Injecting trimebutine resulted in a significant increase in the SO antegrade phasic contraction rate (P = 0.02). Trimebutine decreased the basal pressure of the SO (32.5 vs. 27.5 mmHg), but the difference is not statistically significant (P = 0.11). The effects of trimebutine differed depending on the basal SO motility anomalies involved, but the period of latency was similar (mean 89 s: range 30-240 s). The basal anomalies were an increased basal SO pressure of > 40 mmHg in three patients, a tachyoddia (frequency of phasic contractions (PC) > 10/min) in six patients, prolonged PC (> 10 s) in two patients and an absence of phasic contraction in one patient. The basal pressure of the SO decreased in the three patients presenting with SO hyperpressure, but returned to a normal value in one case. The frequency of the PC decreased to normal in three out of the six patients with tachyoddia. The duration of the PC returned to normal in the two patients with prolonged PC whereas their frequencies increased. Prolonged PC developed in the patient without any detectable phasic contraction. CONCLUSIONS Trimebutine modulates SO motility in various ways depending on the basal SO motility anomaly observed after cholecystectomy. This regulatory effect suggests the existence of encephalinergic control of SO motility.