The human sphincter of Oddi (SO) exhibits phasic wave activity over a 4 to 6 mm segment. Approximately 60% of these waves occur in an antegrade direction, 14% are retrograde, and 26% occur simultaneously. Because cholecystokinin-octapeptide (CCK-OP) stimulates the flow of bile into the duodenum, its effect on SO phasic wave contractions and contraction sequences was evaluated at ERCP manometry. An infused triple-lumen catheter of 1.7 mm outer diameter with side orifices spaced 2 mm apart was stationed in the SO segment so that all three orifices recorded phasic pressure waves. We studied 31 patients with normal ductal anatomy and normal SO pressures. In 21 of these patients CCK-OP (20 ng/kg) was given intravenously after a 2- to 3-minute baseline recording was obtained. Pressure recordings were continued for up to 10 minutes following CCK-OP administration. CCK-OP caused a significant inhibition in the frequency and amplitude of SO phasic waves as well as a significant decrease in basal SO pressure. Before CCK-OP most phasic contractions were antegrade, and after CCK-OP the sequence pattern remained unchanged. We conclude that CCK-OP reduces or transiently abolishes SO phasic contractions but that it does not change their temporal sequence. In addition, CCK-OP produces a decrease in basal SO pressure. These findings suggest that the action of CCK-OP in humans is to inhibit SO phasic activity and reduce SO basal pressure to allow increased flow of bile.