When venous oxygen saturation increases as a result of increased blood flow, changes in venous blood PCO2 and carbon dioxide content may differ because of the Haldane effect. The Haldane effect may also explain increases in gastric mucosal-arterial PCO2 gradient despite major increases in splanchnic blood flow. We re-analysed data from 22 patients after cardiac surgery who were randomized to receive either dobutamine or placebo, and a separate group of patients who received dobutamine for low cardiac output (n = 6). Three different values of gastric mucosal oxygen extraction at baseline were assumed (0.3, 0.5 and 0.7). In nine of 14 patients with both increasing splanchnic blood flow and mucosal-arterial PCO2 gradient, an equal increase in mucosal and total splanchnic blood flow, oxygen consumption and carbon dioxide production together with the Haldane effect would have caused an increase in mucosal-arterial PCO2 gradients from a mean value of 0.53 (SD 0.88) kPa at baseline to 0.68-0.82 (0.89-0.90) kPa (P < 0.01). In the remaining patients, disproportionate changes in flow and metabolism must have been involved in addition to the Haldane effect. We conclude that whenever major changes in mucosal tissue oxygen extraction are likely to occur, an increase in the mucosal-arterial PCO2 gradient may be explained in part or completely by the Haldane effect, and may therefore not reflect worsening perfusion.