Effects of necrotizing agents, blockers of gastric motility, and mild irritants on gastric mucosa and gastric motility were investigated in conscious rats. Gastric motor activity was recorded using a miniature balloon placed in the glandular part of the stomach, which was connected to a pressure transducer and polygraph. Necrotizing agents, such as 96% ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, or 4 M sodium chloride, were given intragastrically through a fistula on the forestomach. One milliliter of these agents produced hemorrhagic bandlike lesions in the corpus mucosa along the long axis of the stomach with the occurrence of a complete inhibition of gastric motility (smooth muscle relaxation). Blockers of gastric motility alone, such as subcutaneous papaverine HCl (50 mg/kg), and intraperitoneal verapamil (20 mg/kg), or mild irritants (1 ml/rat, orally) such as 20% ethanol or 1 M NaCl, which by themselves suppressed gastric motility, have no effect on gastric mucosa and on the inhibited gastric motility induced by necrotizing agents. Bandlike lesions were significantly prevented by pretreatment with 20% ethanol or 1 M NaCl but not with papaverine HCl or verapamil administered 30 min before necrotizing agents. The gastroprotection offered by 20% ethanol or 1 M NaCl was significantly diminished by pretreatment with subcutaneous indomethacin (30 mg/kg), but the inhibited gastric motility was not reversed by indomethacin. These results indicate that it seems unlikely that gastric contractile activity would play a major role in the development and prevention of gastric lesions after the administration of necrotizing agents.