Longitudinal and radial oxygen gradients in the microcirculation due to oxygen release from arterioles show that in some tissues oxygen is primarily supplied by arterioles and secondarily by capillaries. In several tissues, the arteriolar rate of oxygen exit is too large to be explained by diffusion alone, indicating that in these tissues oxygen consumption of the arteriolar wall in vivo is much greater than that shown in in vitro studies of endothelium and vascular smooth muscle, a phenomenon that may be related to the synthesis autocoids by the endothelium in vivo. The functional significance of the high metabolic rate of the arteriolar vessels may be related to the need of providing a metabolic barrier for protecting the parenchymal tissue from high oxygen levels in arterial blood, thus reducing formation of oxygen free radicals in the perivascular tissue, a supposition supported by the finding that the radial oxygen gradient at the microvascular wall and therefore its rate of oxygen consumption are proportional to local blood oxygen partial pressure (pO(2)). Oxygen consumption by the endothelium and/or smooth muscle is also a factor in causing terminal lymphatic pO(2) to have the lowest oxygen level in the tissue, rendering this compartment most vulnerable in hypoxic conditions.