Rats restrained in a cold environment for 3 h developed a high incidence of gastric ulcers. Administration of adenosine receptor agonists prior to a restraint period significantly reduced ulcer formation and severity, and lowered plasma corticosterone levels. This protective effect was blocked by 8-phenyltheophylline, a methylxanthine type adenosine receptor antagonist able to permeate the blood-brain barrier. This finding together with the absolute and relative order of potencies with which adenosine receptor agonists produced their effects suggests that CNS adenosine A1 receptors are involved in blocking and methylxanthines in exacerbating stress-induced gastric pathology.