The effect of exogenous glucose supply by either intrajugular (IJG) or intraduodenal (IDG) infusion at 2.0 mg glucose/kg body weight per min was investigated in four wether sheep (average weight 44 (sd 4) kg) chronically catheterized in the carotid artery and portal veins. Sheep were fed on a dried grass pellet diet hourly using continuous belt feeders. Whole-body glucose irreversible loss (IL) rate, measured with [6-3H[glucose, was increased by 0.5 and 0.8 of exogenous supply for IJG and IDG infusions respectively. Portal glucose utilization, measured by isotope dilution across the portal-drained viscera, was unaffected by additional glucose regardless of the route of glucose supply (P = 0.76 for control ν. glucose infusions) and was a constant proportion of glucose IL (0.28) for all treatments. Portal plasma flow was higher during IDG infusions compared with IJG infusions (1.65 ν. 1.44 litres/min, P=0.055). Circulating total free amino acid concentrations fell during glucose infusions (2146, 1808 and 1683 μmol/l for control, IJG and IDG treatments respectively, P=0.067 for treatment effect) but net portal absorption was not affected by increased glucose supply. Recovery in the portal vein of [1-13C[leucine infused into the duodenum averaged 0.65 and was not affected by increasing glucose supply to the gut tissues. The results show that glucose utilization by gut tissues is responsive to changes in both vascular and luminal glucose supply. The effects of changing gut tissue use of glucose and increased whole body glucose IL on metabolism of nutrients is discussed.