The lack of a rise in global O2 consumption (VO2) after increased O2 supply (DO2) (negative O2-flux test) is an indication of adequate tissue oxygenation. We were interested in whether a negative O2-flux test precludes an improvement in regional tissue oxygenation. The pH of the gastric mucosa (pHi) is considered a sensitive marker for tissue hypoxia. Method. The study was approved by the ethics committee of our hospital. In 12 intensive-care patients with septic shock, gastric pHi was determined (Trip'TGS catheter, Tonometrics) in addition to measuring O2-transport-related parameters via invasive haemodynamic monitoring. Following the initial measurement, a further increase in the O2 supply via volume substitution was attempted in all already hyperdynamic patients with DO2 in the upper-normal range. Results. Volume substitution with 1.246 +/- 594 ml colloid resulted in an increase in pulmonary capillary wedge pressure from 14 +/- 2 mm Hg to 17 +/- 1 mm Hg (P < 0.01). All patients had an increase in DO2 from 755 +/- 192 ml/min.m2 to 846 +/- 236 ml/min.m2 (P < 0.05). There was no significant change in VO2, at 153 +/- 28 ml/min.m2 before and 156 +/- 35 ml/min.m2 after volume administration. However, pHi increased from 7.19 +/- 0.08 to 7.24 +/- 0.08 (P < 0.01). DISCUSSION AND CONCLUSION. The low pHi at the time of the initial measurement shows that regional tissue hypoxia may be present even in patients with an above-normal O2 supply > 600 ml/min.m2. Apparently, the lack of rise in global O2 consumption after increased O2 supply does not exclude a regional improvement in tissue oxygenation. The less invasive pHi measurement is an additional useful monitoring procedure for the optimisation of regional tissue oxygenation in critically ill patients.