To study effects of intrasphincteric injectionsof botulinum toxin on the sphincter of Oddi cyclicmotility and responses to motilin and cholecystokinin,four conscious dogs with duodenal cannula underwent manometry of the common bile duct, sphincter ofOddi, and duodenum. After baseline recording, each doghad intrasphincteric injections of saline or botulinumtoxin. The injections of saline had no effect, whereas botulinum toxin significantly reducedmean basal pressure, amplitude, and motility index ofthe sphincter of Oddi. These effects took place in fourto seven days and reached a maximum in seven to 10 days. The basal pressure returned to thebaseline level in 28 weeks, but the amplitude andmotility index remained low. The pressure parameters ofmotilin-induced premature phase III-like activity also decreased, but action of cholecystokinin wasnot affected. These results indicate that the botulinumtoxin injections reduce sphincter of Oddi phasiccontractile activity for a prolonged period oftime.