The effect of tidal volume (VT) on gas exchange and oxygen delivery (DO2) was studied in nine patients with adult respiratory distress syndrome (ARDS) and in 10 postoperative open-heart surgery patients (CABG). During controlled mechanical ventilation, VT was initially 10 to 12 ml/kg, followed by an increase and reduction of 25% (1.25 VT and 0.75 VT, respectively). In both groups of patients, dead space (VD) correlated strongly with VT (p < 0.001), while the VD/VT ratio was independent of VT. PaO2 tended to increase in CABG patients and decrease in ARDS patients at 1.25 VT. Arterial oxygen saturation (SaO2) did not change at 1.25 VT but decreased at 0.75 VT (p < 0.001) in the ARDS group. Venous admixture (QS/QT) decreased with 1.25 VT and increased with 0.75 VT (p < 0.001). A relatively larger increase in cardiac output compensated for the increased QS/QT and the reduced SaO2, resulting in significantly higher DO2 with 0.75 VT (p < 0.01). A lower VT resulted in improved balance between pulmonary gas exchange and whole body oxygen supply.