Effects of domperidone on gastric emptying and gastric, duodenal and gallbladder motility were investigated. Intravenous injection of domperidone 2 mg/kg produced an acceleration of gastric motility without increase in the tone while a marked increase in the amplitude of peristaltic waves with a slight decrease in frequency was observed. Domperidone also produced an acceleration of duodenal and gallbladder motility. Domperidone produced an acceleration of transit of stomach contents in some cases, while in others gastric emptying was inhibited. This difference of the effect may be due to the previous tone of the pylorus. The excitatory action of domperidone on gastrointestinal motility was suppressed to some degree after cervical vagotomy or vagus cooling and markedly inhibited by atropine. Tetrodotoxin reduced the excitatory effect of domperidone but did not abolish. Therefore, it is presumed that domperidone stimulates, at least in part, the gastrointestinal muscle itself as well as cholinergic neurons in the gastrointestinal wall or cholinergic receptors of the gastrointestinal muscle and that domperidone may also have a central nervous system stimulant action. On the other hand, domperidone appears to act directly on the gallbladder muscle.