OBJECTIVE: To determine if air introduced directly into the lumen of a hollow viscus can be used instead of fluid in a Silastic balloon to estimate gastrointestinal mucosal PCO2. DESIGN: Prospective, unblinded comparison of two methods of mucosal PCO2 measurement. SETTING: Animal surgery suite at a large, university-affiliated medical center. INTERVENTIONS: Standard, commercially available, tonometric catheters were positioned in the ileum (n = 4) or the stomach and ileum (n = 12) of anesthetized, immature Yorkshire swine. Using gas-tight purse-string sutures, plastic cannulas were inserted into the lumen of the stomach (n = 12) and the lumen of a 10-cm isolated segment of ileum (n = 16). Data were collected after equilibration periods of 30 or 60 mins. Before each equilibration period, the "air tonometers" (i.e., the lumens of the stomach and/or the isolated ileal segment) were lavaged with 200 mL (stomach) or 20 mL (ileum) of air. In group 1 (n = 4) and group 2 (n = 3), graded degrees of mesenteric hypoperfusion were achieved by mechanical mesenteric occlusion or pericardial tamponade, respectively. In group 3 (n = 8), graded degrees of respiratory acidosis were induced. At various intervals, PCO2 was determined simultaneously in arterial blood, gastric air, saline from the gastric tonometric balloon, ileal air, and saline from the ileal tonometric balloon. MEASUREMENTS AND MAIN RESULTS: In pigs with ischemia created by mesenteric vascular occlusion (group 1), there was a moderate correlation between PCO2 values in air samples from the ileal lumen and samples of saline from the standard tonometer (r2 = .61, p < .001). In pigs with mesenteric ischemia secondary to pericardial tamponade (group 2), air and saline tonometry were well-correlated in the stomach (r2 = .71, p < .001) and ileum (r2 = .83, p < .001). In pigs with normal mesenteric perfusion (group 3) and PaCO2 > 40 torr (5.3 kPa), PaCO2 correlated with ileal mucosal PCO2, determined using air (r2 = .93, p < .001) or saline (r2 = .91, p < .001) tonometry, or gastric mucosal PCO2, determined using air (r2 = 1.00, p < .001) or saline (r2 = .97, p < .001) tonometry. Values obtained by air tonometry were highly correlated with values obtained using standard saline tonometry in the stomach (r2 = .98, p < .001; bias = -5 +/- 5 torr [-0.65 +/- 0.65 kPa]) or ileum (r2 = .96, p < .001; bias = 1 +/- 9 torr [0.13 +/- 1.17 kPa]). CONCLUSIONS: a) Under stable hemodynamic and respiratory conditions, air tonometry (which, in theory, can be performed using a conventional nasogastric or nasoenteric feeding tube) estimates gastrointestinal mucosal PCO2 as accurately as standard saline tonometry in the stomach or ileum; b) respiratory acidosis leads to tissue hypercarbia, a phenomenon that must be considered when tonometry is used to guide therapy in the clinical setting; c) under stable, nonischemic conditions, gastric or intestinal tonometry can be used to estimate PaCO2.