According to the traditional view gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanisms of action--antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents--thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing yield contradictory clinical results; morning and bedtime single administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.