Corticotropin-releasing factor (CRF) administered into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit, but most markedly increased large bowel transit in a dose-related fashion in freely moving rats. Inhibition of gastric emptying induced by central administration of CRF was completely abolished by pretreatment of the animals with either the ganglionic blocking agent chlorisondamine or the opioid antagonist naloxone, or by noradrenergic blockade with bretylium, but not by truncal vagotomy. Either chlorisondamine, naloxone, or vagotomy--but not bretylium--reversed the inhibitory effect of central CRF on small bowel transit. Chlorisondamine or vagotomy, but neither bretylium nor naloxone, abolished the stimulatory effect of central CRF on large bowel transit. Neither hypophysectomy nor adrenalectomy altered the gastrointestinal motor responses induced by central administration of CRF. Intraperitoneal administration of CRF also significantly inhibited gastric emptying and stimulated large bowel transit but did not alter small bowel transit. These peripheral effects of CRF were not prevented by blockade of autonomic efferents with bretylium or chlorisondamine. It is concluded that (a) CRF acts within the central nervous system to delay gastric emptying, to inhibit small bowel transit, and to increase large bowel transit in freely moving rats and (b) CRF exerts these biological actions by modulation of the autonomic nervous system and, in part, by opioid pathways.