Changes in basal- and pentagastrin-stimulated gastric acid, pepsin secretion as well as gastric mucosal histidine decarboxylase activity were examined in 4- to 21-month-old pyloric ligated Fischer-344 rats. In addition, serum gastrin levels, gastric mucosal DNA, and RNA content were determined in these rats. The results revealed that whereas acid secretion decreased progressively with age, pepsin output increased between 4 and 14 months of age and then decreased sharply. Serum gastrin levels decreased progressively with age, and 3 h of pyloric obstruction produced no apparent change in serum gastrin levels in any of the age groups. Gastric mucosal weight, DNA, and RNA content in 4-month-old rats were not significantly different from those of 14-month-old animals. However, in 21-month-old rats, each of these values were found to be significantly lower than in their 4- or 14-month-old counterparts. A single injection of pentagastrin (250 micrograms/kg) significantly stimulated acid and pepsin secretion (45-52%) in 4-month-old rats, but not in 14- and 21-month-old animals, when compared with the corresponding saline-injected controls. Gastric mucosal histidine decarboxylase activity increased steadily between 4 and 21 months of age. Pentagastrin caused a significant 78% stimulation in histidine decarboxylase activity in 4-month-old rats, but had no effect on the enzyme activity in 14-month-old animals, when compared with the corresponding saline-injected controls. However, in 21-month-old rats, pentagastrin inhibited histidine decarboxylase activity by 55% when compared with the saline-injected controls. It is concluded that a) aging decreases capacity of the gastric mucosa to secrete acid and pepsin, b) in aged rats, decreased acid and pepsin output could in part be attributed to mucosal atrophy; c) responsiveness of the gastric mucosa to pentagastrin decreases with age; and d) in aged animals, gastric acid secretion is not regulated by histamine.