The effects of upper small intestinal perfusion with iso-osmolar or hyperosmolar polyethylene glycol (PEG) solutions on maximal gastric acid secretion stimulated by intravenous pentagastrin was investigated in Sprague-Dawley rats. The animals were provided with a chronic gastric fistula, a gastroenterostomy and a 4-cm duodenal loop anastomosed end-to-side to the jejunum. The oral end of the duodenal loop was closed and intubated for infusion of various solutions. Saline was infused in the control experiments, 2 ml h-1. In the test experiments, saline was replaced with PEG, 300, 900 or 1,200 mosm.kg-1. Duodenal perfusion with iso-osmolar PEG, 300 mosm-kg-1, did not alter maximal acid secretion. Duodenal perfusion with hyperosmolar PEG 900 or 1,200 mosm.kg-1 significantly inhibited the stimulated 2-hour acid output by 47 and 48% respectively (p less than 0.01). Indomethacin, an inhibitor of the prostaglandin synthesis, did not alter the stimulated acid secretion, and the inhibitory influence on acid secretion of duodenal perfusion with PEG 1,200 mosm.kg-1 as not affected by the drug.