The arterio-venous difference technique is now well established in the study of organ and tissue metabolism. This technique requires samples to be obtained of the arterial blood supplying and the venous drainage from a tissue, together with a measurement of the blood flow through the tissue. The technique is most appropriate when the arterial concentration and tissue metabolism of a substance are constant, and when the blood flow is stable. If these criteria are not satisfied, care is needed in the interpretation of the results obtained. It should be recognized that the arterio-venous difference technique only measures the net exchange of a substance with the tissue, and that tracers are needed if unidirectional flux needs to be estimated. The other factors which must be borne in mind when intending to use this technique are the transit times of blood and the substance of interest through a tissue, the volume of distribution of the substance in the tissue, and the possibility that the venous samples obtained are derived from a mixture of different tissues.
