The effect of the H2-receptor antagonist ranitidine on pancreatic exocrine secretion was studied in the rat. In anaesthetized animals with acute fistulas pancreatic secretion was induced by central (2-deoxy-D-glucose, 2-DG) or peripheral (acetylcholine) cholinergic stimulants and by cholecystokinin and secretin. In some experiments cimetidine was used as a reference compound. Ranitidine (20 mg X kg-1 intraperitoneally) did not change neither basal secretion nor the response to the combined hormonal stimulation. On the contrary, it significantly increased 2-DG and acetylcholine-stimulated secretion, whereas cimetidine (100 mg X kg-1 intraperitoneally) inhibited the pancreatic response to 2-DG. The different behaviour of the two H2-antagonists suggests that the effect of ranitidine is independent of the H2-receptor blockade and most probably connected with the cholinergic-like action of the drug.