Topical 16,16-dimethyl (dm) prostaglandin E2 produces an alkaline secretion from the canine stomach. This study attempts to assess whether this prostaglandin-induced secretion might have a cytoprotective role. Chambered ex vivo perfused wedges of canine stomach were divided into equal halves: a control and test side. The mucosa of each half was sequentially exposed to isosmotic hydrochloric acid, 20 microgram of 16,16 dm PGE2 in acid, 20 mmol aspirin + 20 microgram of dm PGE2 in acid then isosmotic acid. The test side received 40 mmHg pneumatic counterpressure to reduce the prostaglandin-induced fluid movement before, during and after the aspirin exposure. The mucosal lesions produced on each side were graded 0 to 14. If prostaglandin exerts its cytoprotective effect by stimulating an alkaline secretion, elimination of that secretion with counterpressure should prevent a cytoprotective action. Nine dogs were studied. Topical prostaglandin increased transmucosal fluid movement from 10 microliter/min to 65 microliter/min. Counterpressure decreased this volume flow by 50 per cent (P < 0.01); it also decreased mucosal blood flow on the test side by 20 per cent (P < 0.05). The lesions on the counterpressure side were worse 2.0 +/- 0.6 v. 0.8 +/- 0.3 (P < 0.01). Thus the greater damage in the counterpressure group could have been caused by diminished fluid movement or by reduced blood flow or a combination of both factors. Although this study cannot distinguish between these possibilities, it seems like that the prostaglandin-induced alkaline secretion has a cytoprotective role.