In healthy tissues, decreases in oxygen delivery (QO2 = cardiac output X arterial O2 content) do not lower oxygen consumption (VO2) because tissue O2 extraction increases proportionately. When delivery is reduced below a critical threshold, VO2 falls because tissue extraction exceeds a critical threshold, and cannot compensate for the reduction in delivery. In the adult respiratory distress syndrome and perhaps in septicemia, tissue extraction capacity is impaired, leading to O2 supply dependency despite normal or increased overall delivery. This pathologic supply dependency could be caused by a loss in autoregulatory capacity, by disrupted blood flow distribution secondary to peripheral microembolization, or to other factors interfering with efficient tissue distribution of QO2 with respect to VO2. Alternatively, the increased VO2 may be consumed in biochemical pathways not associated with ATP production, or in the production of oxygen radicals or hydrogen peroxide. To the extent this abnormal dependence of VO2 on QO2 reflects tissue hypoxia, clinical interventions which decrease systemic delivery should be evaluated with regard to possible deleterious effects on organ system function.