The role of luminal acid and the influence of the antisecretory action of verapamil in stress ulcer prevention in rat stomachs have been studied. Intraperitoneally injected verapamil, 4 mg kg-1, inhibited gastric acid secretion and ulcer formation, however, a 2 mg kg-1 dose, which did not significantly influence acid output, also had an antiulcer effect. Intraperitoneal injection of bethanechol, 1.2 or 3.6 mg kg-1, increased gastric acid output, but did not influence stress-induced ulcer formation. Oral administration of HCl, 25 or 50 mu equiv, aggravated stress ulceration in a dose-dependent manner; this lesion-worsening effect was prevented by pretreatment with verapamil or bethanechol. The gastric luminal acid content in 2 h pylorus-ligated rats was similar in the groups given either bethanechol or HCl. These findings indicate that the antisecretory action of verapamil may not account for its antiulcer effect. It is suggested that endogenous and exogenous luminal acid may have different influences on stress ulcer formation.