Red blood cell (RBC) transfusion is usually administered to improve oxygen delivery (DO(2)) in order to sustain tissue oxygen demand. However, this practice is not supported by firm clinical or experimental data. Using a randomized two-period crossover design, this study compared the efficacy of "fresh" RBC transfusion and increased blood flow to restore tissue oxygenation in oxygen supply-dependent conditions. In 12 ketamine-anesthetized mongrel dogs submitted to nonpulsatile normothermic cardiopulmonary bypass, DO(2) was reduced by a progressive decrease in pump flow. DO(2) dependency was defined as an O(2) uptake (V O(2)) decrease by more than 15% from baseline value. Then, intervention consisted of a 40% increase in DO(2) obtained either by transfusion of "fresh" dog's RBC (stored < 3 d) or by increase in pump flow. Animals received both interventions sequentially in a random order, while O(2) saturation was maintained constant. In O(2) supply-dependent conditions, rising pump flow from 1.6 +/- 0.4 to 2.7 +/- 0.7 L/ min increased DO(2) from 5.4 +/- 1.1 to 9.0 +/- 1.3 ml/kg/min (p < 0.01) and V O(2) from 3.5 +/- 0.4 to 4.1 +/- 0.5 ml/kg/min (p = 0.02). "Fresh" RBC transfusion, which increased the hemoglobin concentration from 6.4 +/- 0.9 to 11.1 +/- 1.3 g/dl, increased DO(2) from 5.4 +/- 1.2 to 9.0 +/- 1.4 ml/kg/min (p < 0.01) and V O(2) from 3.6 +/- 0.4 to 4.1 +/- 0.5 ml/kg/min (p = 0.02). There was no difference in V O(2) resulting from both interventions. In oxygen supply-dependent conditions, "fresh" RBC transfusion and increased blood flow are equally effective in restoring tissue oxygenation.