Hepatic metabolic balances derived from arterio-hepatic-venous substrate differences and hepatic blood flow exhibited similar results during fructose infusion (10 g/5 min., 0.5 g/kg x h) as compared to those from the isolated perfused organ: a portion of 55% of splanchnic fructose uptake was accountable for splanchnic glucose production, 25% for splanchnic lactate and pyruvate production and 20% for glycogen - of fat - synthesis and endoxidation. In account of this hepatic metabolism of fructose, glucose homeostasis and insulin secretion almost maintained. However, the small insulin response did not reduce hepatic free fatty acid utilization to such an extent as to increase pyruvate oxidation. Accordingly, splanchnic production of lactate and pyruvate, descending from fructose was enhanced. Since hepatic-venous lactate: pyruvate substrate ratios did not change, the rise of the arterial redox couple could not be due to hepatic fructose metabolism. According to the findings from the isolated perfused organ, fructose seemed to be phosphorylated at a rate which was found to be 2 to 3-fold that of glucose as calculated from splanchnic utilization rates. This high rate of fructose uptake was reduced with increasing insulin levels. The rapid ATP breakdown was followed by an increment of splanchnic oxygen consumption. The larger energy demand seemed to be satisfied by an enhanced endoxidation of free fatty acids. Since diabetics failed to increase their insulin production, their hepatic fructose phosphorylation rate and consequently their hepatic oxygen demand were not limited. Preliminary results concerning metabolic balances from the human forearm during a steady state of fructose supply, underline the notion that fructose has some effects on intermediary metabolism of skeletal muscle. Accordingly, in juvenile diabetics an enhancement of glucose-, lactate- and pyruvate-uptake could be demonstrated.