Oxygen transport from blood to the mitochondria is dependent on oxygen gradients. The interstitial or extracellular pO(2), measured by the phosphorescence-decay method, is indicative of these driving forces and the amount of oxygen available to the mitochondria. Diverse protocols for sampling tissue pO(2) show that measurements sampling only interstitial pO(2) levels provide a reliable measurement of the tissue pO(2) level. Present findings lead to the hypothesis that tissue has a fairly uniform interstitial fluid pO(2) level and that local inhomogeneity due to the presence arteriolar and venular vessels is smoothed out by the steep gradients at the microvascular walls.