The effect of substance P on gastric motility was studied in conscious dogs by means of strain gauge force transducers chronically implanted on the gastric body, antrum, and a vagally-denervated fundic pouch. Intravenous infusion of substance P in the interdigestive state induced phasic contractions in the pouch and antrum. Atropine inhibited these contractions in the pouch and antrum. Hexamethonium enhanced substance P-induced contractions in the gastric antrum, but reduced those in the pouch. Pretreatment with phentolamine, propranolol, or naloxone did not affect substance P-induced contractions in the pouch and antrum. The intact gastric body scarcely reacted to substance P. Mean systemic blood pressure was lowered by substance P-infusion, but there was no dose-dependency in the reduction of the blood pressure, nor was it affected by the pretreatment with atropine or hexamethonium. These results suggest that 1) the vagal innervation influences the effect of substance P on motility in the gastric body, and that 2) substance P may stimulate postsynaptic excitatory cholinergic and presynaptic inhibitory neurons simultaneously in the gastric antrum.