The effects of caerulein on gastric motility in urethane-anesthetized rats were studied. Caerulein administered into the lateral cerebral ventricle (i.c.v.) and jugular vein (i.v.) caused predominantly an inhibitory effect on gastric motility but sometimes an excitatory or a biphasic effect. The inhibitory response was reduced after vagotomy and/or splanchnicotomy, or after guanethidine. The remaining inhibitory response was abolished by tetrodotoxin, but was resistant to atropine and guanethidine. The excitatory response was abolished by atropine. Discharges of the gastric branch of the vagus nerve were decreased by i.v. injection of caerulein but increased by i.c.v. injection, whereas those of the splanchnic nerve were increased by both i.v. and i.c.v. injection. These results suggest that caerulein causes an inhibition of gastric motility by centrally stimulating vagal non-adrenergic inhibitory nerves and splanchnic adrenergic nerves and inhibiting vagal cholinergic nerves, and by peripherally stimulating non-adrenergic inhibitory neurons of the myenteric plexus. This peptide causes an excitation by stimulating cholinergic neurons of the myenteric plexus.