Gastric acid secretion in response to chemical stimulation and to mechanical stimulation was investigated in adult and old mice. The protein expression of a proton pump (H(+)-K(+)-ATPase), a marker of parietal cell function, was determined by Western blotting. Acid secretion was stimulated by histamine (500 and 1000 microg/kg) or carbachol (10 and 20 microg/kg). To investigate the response to mechanical stimulation, the stomach was distended by an intragastric injection of isotonic saline (0.5, 1.0, 1.5, and 2.0 ml). Administration of two doses of histamine produced a dose-dependent increase in acid secretion in adult mice, whereas a higher dose of histamine failed to produce a further increase in old mice. Gastric acid secretion, whether produced by carbachol or mechanical stimulation, did not differ between the two age groups. The protein expression of H(+)-K(+)-ATPase was significantly lower in old mice than in adult. Insofar as histamine increases acid secretion via the cyclic AMP (cAMP) pathway in parietal cells, while carbachol and gastric distention do so via the calcium signaling pathway, the cAMP signaling pathway may be more susceptible to aging than the calcium signaling pathway. The decrease in the secretory capacity of acid secretion in the old mice may be partly attributable to a decrease in parietal cell function, as shown by decrease in H(+)-K(+)-ATPase protein expression.