The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin-induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum. Administered intracerebroventricularly at doses of 20 and 100 ng/kg in fasted dogs, CRF suppressed for 4-5 h the gastric cyclic migrating motor complex. A similar dose (100 ng/kg) administered intravenously was inactive. Corticotropin-releasing factor administration by the intravenous route at 100 ng/kg did not alter the cyclic plasma motilin and somatostatin variations associated with the cyclic gastric motor events. During the blockade of antral migrating motor complex induced by intracerebroventricular administration of CRF, cyclic peaks of plasma motilin were absent whereas those of somatostatin persisted. The gastrointestinal migrating motor complex induced by the intravenous administration of porcine motilin (0.25 microgram/kg) was abolished when motilin was injected 2 h after the intravenous administration of CRF (100 ng/kg), whereas a similar dose of CRF administered intracerebroventricularly did not abolish the antral and jejunal motor responses to motilin. It is concluded that in fasted dogs, CRF administered centrally affects the interdigestive gastric motility and the release of motilin but not that of somatostatin. These results also suggest that the intracerebroventricular CRF-induced blockade of motilin release is responsible for the inhibition of gastric migrating motor complex and circulating CRF is able to affect the gastric motor response to porcine motilin through a peripheral mechanism that does not involve somatostatin and motilin secretion.