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Gastric intramucosal pH (pHi) is often calculated by the Henderson-Hasselbalch equation, using arterial plasma [HCO3-]ap and PCO2 measured in saline obtained from a silastic balloon tonometer after equilibration in the lumen of the stomach. A pHi value less than approximately 7.3 pH units is often taken as evidence of intestinal ischemia. An alternative measure is tissue PCO2 (PtCO2)-PaCO2 difference [P(t-a)CO2]. The idea is that PtCO2 will increase slightly relative to PaCO2 as O2 supply decreases, and then increase strikingly when flow decreases to a critical value, because of liberation of CO2 from tissue Hco3- by anaerobically generated strong acid. A third method is arterial plasma pH (pHap)-pHi difference [pH(ap-i)]. We used mathematical simulations to test the hypotheses that calculated pHi is independent of arterial acid-base status; and pH(ap-i) provides the same information as does P(t-a) CO2. Using the Van Slyke version of the arterial whole blood [standard base excess] ([SBE]aWB) equation, it was found that a change in [SBE]aWB at constant PaCO2 and constant PtCO2 produces a change in calculated pHi (P = 0), such that the relation between changing [SBE]aWB and changing pHi is predictable by a single polyomial equation (R2 = .999). pH(ap-i) avoids this confounding influence of [SBE]aWB. However, it was further shown that pH(ap-i) can be associated with a wide range of P(t-a)CO2, depending on the magnitude of pH(ap-i), and on the PaCO2 at which P(t-a)CO2 is measured. We conclude that P(t-a)CO2 is a more reliable index of gastric oxygenation than is pHi alone or pH(ap-i).