Lung metabolic functions include the interaction of microvascular endothelium with blood-borne substances such as physiologically important amine, eicosanoid, and peptide hormones and drugs. This activity is mediated by endothelial transport systems and enzymes which either synthesize or degrade these substances. Because they can alter the hormone content of aortic blood, these functions play a role in homeostasis, and their disturbance has been implicated in the pathogenesis of several forms of lung injury and disease. Both steady-state infusion and single injection, multiple indicator dilution techniques have been applied to measure endothelial metabolic functions in the intact lung. Considerable progress has been made in development of mathematical models for the processes, and their application has been tested both under normal conditions and also when the lung is perturbed experimentally. Unique experimental challenges are presented by measurement of metabolic functions in vivo, when steady-state infusion techniques cannot be used because systemic toxicity could result. In this case, the bolus injection approach has been used, with some success, both in laboratory animals and man. Although major challenges remain, their solution is essential if we are to apply knowledge of endothelial cell function in vitro to understanding lung microvascular physiology and pathophysiology in the intact animal.