This study was undertaken to investigate the site of origin of vagal reflexes which cholecystokinin (CCK) activates to cause reflex inhibition of gastric motility. In the anaesthetized ferret, close intraarterial injections of CCK-8 (100 pmol) caused a short latency increase in duodenal contractile activity; antral motor responses to CCK were variable, often comprising excitation followed by inhibition. The corpus, in contrast, consistently showed a decrease in pressure which lasted 2-3 min before returning to prestimulus levels. Similar responses to CCK-8 were seen in guanethidine (5 mg/kg) treated preparations, indicating that release of noradrenaline was not responsible for the relaxatory responses observed. After bilateral cervical vagotomy the duodenal response was unchanged, but the antrum showed consistent monophasic increases in tone. The response of the corpus was reversed to one of excitation, which was significantly different from prevagotomy responses (P less than 0.0001). In 10 experiments, corpus responses to CCK were tested after removal of the intestine and again after removal of the antrum. Upon removal of these segments the inhibitory motor response to CCK was reversed to one of excitation (P less than 0.01). Corpus relaxation in response to duodenal distension was significantly smaller (P less than 0.05) than that to CCK despite higher duodenal pressures during distension. Minimizing intraantral pressure changes by means of an isotonic reservoir system did not affect the response of the corpus to CCK administration. The data indicate that the inhibition of gastric motility by CCK is mediated by a direct vagal reflex and is not secondary to motility changes.(ABSTRACT TRUNCATED AT 250 WORDS)