The effect of aging on gastric and duodenal mucosal prostaglandins has not been reported. Gastric and duodenal mucosal prostaglandin concentrations were measured in 46 healthy adults, 35 of whom were relatively young (21-40 years old) and 11 of whom were considerably more elderly (aged 52-72 years). Mucosal biopsy specimens were obtained endoscopically from the fundus, antrum, duodenal bulb, and postbulbar duodenum, and extracts were assayed for prostaglandin F2 alpha and E2 concentrations by radioimmunoassay. Older age was associated with significantly lower fundic, antral, and post-bulbar duodenal prostaglandin concentrations. A second experiment was performed in 20 additional subjects (9 younger, 11 older) to determine whether lower mucosal concentrations in older subjects were reproducible and, if so, whether reduced gastric mucosal prostaglandins would have a physiological counterpart, namely increased gastric acid secretion. As in the original experiment, fundic, antral, and postbulbar mucosal prostaglandin levels were significantly lower in older subjects than in younger subjects. Mean basal acid output was significantly higher in older than younger subjects (9.8 +/- 2.5 vs. 4.8 +/- 1.6 mmol/h). It is concluded that gastric and duodenal prostaglandin concentrations decline with aging in humans and that the decline in fundic mucosal prostaglandins is associated with an increase in gastric acid secretion.