Tonometric measurement of an elevated intragastric Pco2 and a decreased calculated gastric intramucosal pH can be used to detect gastric mucosal ischemia, provided that intraluminal production of CO2 through acid buffering by bicarbonate is avoided by adequate acid secretion suppression. If the diffusion rate is known, steady state Pco2 can be calculated when measurement intervals are used that are shorter than needed for complete equilibration. The CO2 diffusion might be influenced by the choice of acid-suppressive drugs, since some of them inhibit gastric carbonic anhydrase (CA) and CA facilitates diffusion of CO2/bicarbonate over the gastrointestinal mucosa. We therefore performed gastric Pco2 tonometry, using acid-suppressive regimens with and without CA inhibition. The diffusion rate of CO2 in a gastric tonometer was studied in healthy volunteers, following intravenously administered ranitidine (group I, N = 8) or ranitidine plus pirenzepine (group II, N = 12), a muscarinic antagonist with CA inhibiting capacities. Measurement intervals were 10, 20, 30 and 60 min. Neither the diffusion rate of CO2 (k = 0.13 +/- 0.02/min in group I and 0.11 +/- 0.02/min in group II), nor the steady-state Pco2 (38 +/- 3 mm Hg in group I and 40 +/- 4 mm Hg in group II), nor the gastric-blood differences in Pco2 and pH differed between groups. These results indicate that diffusion of CO2 into the tonometer balloon is independent of CA and thus of the type of gastric acid secretion inhibition.