The gastric anti-secretagogue effects of cimetidine (a histamine H2-receptor antagonist) and of atropine (a non-selective muscarinic receptor antagonist) and pirenzepine (a selective muscarinic M1-receptor antagonist) were examined in conscious gastric fistula rats both under basal conditions and after stimulation with maximal doses of pentagastrin and histamine. Cimetidine blocked basal as well as stimulated acid secretion. The cimetidine dose-response curves and the calculated ED50 values were similar in the different experimental situations. Atropine blocked equally effectively the basal and the stimulated acid secretion. The antisecretagogue and pupil dilating effects were compared. The ED50 values for the anti-secretagogue effect and for the pupil dilating effect were in the same range though not identical. Pirenzepine blocked acid secretion, whether basal or stimulated, with similar potency. It was much more potent to block acid secretion than to cause pupil dilatation. The greater potency of pirenzepine to block acid secretion than to cause pupil dilatation suggests that the cholinergic pathway of acid secretion involves neuronal muscarinic M1-receptors within the intramural ganglia of the stomach wall. In conclusion, cimetidine, atropine and pirenzepine effectively blocked basal as well as pentagastrin- and histamine-stimulated acid secretion, indicating that both histamine and acetylcholine are important in the control of the parietal cell. Histamine has been claimed to be the final common chemical mediator of acid secretion. This view is at odds with the fact that muscarinic blocking agents also inhibit basal and stimulated acid secretion.