When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically.