Quantitative measurements of the umbilical uptake of a variety of substrates were made in the ovine fetus in both the fed state and after 5 days of maternal fasting. Blood flow was measured in both study periods using the antipyrine method, with the simultaneous measurement of umbilical vein and arterial concentrations of glucose, oxygen, and 25 amino acids in whole blood. Umbilical blood flow and fetal oxygen consumption remained unchanged between the fed and fasted states. Umbilical glucose uptake decreased from a mean of 6.85 to 2.79 mg X kg-1 X min-1 with a concomitant fall in the glucose:oxygen quotient from a mean of 0.70 to 0.31. Whereas the majority of gluconeogenic amino acids decreased in concentration in the maternal circulation during fasting, the branched-chain amino acids, as well as 3-methylhistidine, increased. In contrast the majority of amino acids in the fetal arterial circulation either increased significantly or remained unchanged in concentration. Although the fetal excretion of urea increased by 70% during the period of maternal fasting, the total fetal uptake of nitrogen in the form of free amino acids via the umbilical circulation did not change (1,337 vs. 1,027 mg X kg-1 X day-1). These data suggest that the supply of amino acids from the mother to the fetus does not change dramatically during maternal fasting. Therefore, the fetus must either catabolize amino acids previously destined for fetal tissue synthesis and/or begin catabolizing its own protein stores.