The role of endogenous opioids and opioid receptors in the control of migrating myoelectric complexes (MMCs) was studied in conscious dogs implanted with silver-silver chloride electrodes. In normal fasted dogs, MMC cycle times were 103 +/- 7 min in the duodenum. During naloxone infusion (1-2 mg/kg iv, then 0.2-1.0 mg.kg-1.h-1 iv) cycle times increased to 219 +/- 29 min (P less than 0.01). Naloxone (2 mg/kg iv, then 1 mg.kg-1.h-1 iv) had no effect on the response of the small intestine to bethanecol (5 mg sc) or to feeding. Pretreatment with naloxone (2 mg/kg iv) 5 min before the administration of motilin (400-500 micrograms/kg iv) did not block the initiation of MMCs by motilin. In separate experiments, animals were pretreated with the positive or negative isomer of the opioid receptor antagonist WIN-44,441 (0.2 mg/kg iv) 5 min before morphine administration. The negative isomer binds to opioid receptors whereas the positive isomer does not. The negative but not the positive isomer antagonized all effects of morphine on intestinal myoelectric activity. These studies suggest that endogenous opioids and opioid receptors may play a role in control of the initiation of MMCs and that motilin and exogenous opioids act via different mechanisms to initiate MMCs.