The aims of our study were 3-fold: (1) to determine the effect of an acute cold pressor test on vagally stimulated gastric acid secretion, (2) to evaluate whether adrenergic blockers are able to prevent the stress-induced alterations of vagally stimulated gastric acid secretion, and (3) to assess the effect of stress and adrenergic blockers on serum levels of vagally stimulated pancreatic polypeptide and gastrin. Twenty-eight studies were carried out on 7 healthy subjects, each one of them being evaluated on four separate occasions. Active (4 degrees C) or control (37 degrees C) cold pressor tests were applied in random order after an interval of 15 min following completion of a vagal stimulation represented by modified sham feeding. Each stressful stimulus was preceded by an intravenous bolus plus an infusion of either adrenergic blockers (propranolol and phentolamine) or placebo. Modified sham feeding significantly stimulated gastric acid secretion and circulating hormonal levels, compared to basal values. Cold pressor test significantly stimulated gastric acid secretion 30 min after the beginning of the stressful stimulus. This stress-induced secretory response was completely prevented by infusions of adrenergic blockers. No effect was induced by stressful stimuli or by adrenergic blockers on human pancreatic polypeptide and gastrin circulating levels. The present study demonstrates that the cold pressor test induces a late increase of vagally stimulated gastric acid secretion suggesting a possible role mediated by adrenergic neural pathways.