We have attempted to show a number of uses of tracers both as enhancing the information obtained in arterio-venous difference studies and in allowing the collection of data on hepatic metabolism--glucose production, glycogen formation, etc. in a noninvasive fashion. We have demonstrated, using these methods, that (1) The fractional extraction of glucose by the liver during glucose loading is about 5%; (2) This extraction can lead to significant hepatic glucose uptake (25 g after 100 g glucose load); (3) Only some of this glucose (10 g) is taken up directly into glycogen; (4) The remainder of the glycogen formed following a glucose load (15 g) is synthesized by gluconeogenetic pathways; (5) This gluconeogenesis takes place primarily from lactate which is taken up avidly by the liver--50-60% extracted; (6) This lactate arises from the gut (40%) and from the liver itself (at least 10%) with the remainder from other peripheral obligate lactate producing tissue; (7) It was also shown that the amount and pathways of hepatic glycogen production after oral and intravenous glucose loading is very similar and that the major effects on glucose tolerance take place in peripheral tissues such as the forearm.