Although until recently the reduction of gastric acid secretion was the primary aim in the treatment of peptic ulcer disease, it is now recognised that the presence of Helicobacter pylori and not only acid is required to produce duodenal ulcer. Accordingly, the part played by gastric acid has been relegated to the contributor to the effects of H pylori infection. Recent research into the pathogenesis and treatment of peptic ulcer disease suggests the locus of receptors for acid stimulants, such as acetylcholine, histamine and gastrin, to be the immune cell in the lamina propria of gastric mucosa, and not the parietal cell. Thus the effects of acid stimulants, as well as those of mediators of other gastro-intestinal functions, such as oesophageal and gastroduodenal bicarbonate secretion, may be directly transmitted to the effector cells via macrophages and plasma cells. Nitric oxide (NO) may be the agent mediating the interaction between immune and epithelial cells. If these findings are validated and confirmed in man, they may pave the way for new approaches to the treatment of acid-related disorders, resulting in therapeutic strategies that do not necessitate the eradication of H pylori.