An oral gavage of either 3, 1, or 0.1 mmoles of glucose was given to rats under standard feeding conditions or food deprived for 24 hr. The blood flow of the portal and suprahepatic veins as well as the hepatic balances for glucose, lactate, alanine and pyruvate were estimated. In fed rats, after the administration of an oral 3 mmoles load, the liver actually released 310 mumoles of glucose and 90 of lactate, amounts that could be accounted for by the uptake of alanine (148 mumoles) and small loss of glycogen (275 mumoles of glycosyl residues). In starved rats, however, the liver took a very high proportion (c. 71%) of the glucose absorbed, both as glucose (780 mumoles), lactate and pyruvate (892 mumoles) or alanine (134 mumoles). The synthesis of glycogen was considerably limited, accounting for only 205 mumoles, and leaving practically one mmol of glucose equivalent energy available for liver function and the synthesis of other compounds. Practically all glycogen was synthesized directly from glucose, since the synthesis from 3 C carriers was less than a 5%. Smaller gavages (1 or 0.1 mmoles) resulted in a much lower liver uptake activity. The strikingly different activity of the liver with respect to the available glucose and 3 C fragments could not be explained alone by the circulating levels of these compounds, suggesting a very deep influence of the intestine in hepatic function. The liver plays a very passive role in fed animals, with a very small involvement in the disposal of a glucose load, whereas it takes on an important role when the overall availability of energy is diminished.