[U-14C]glutamine and [6-3H]glucose were infused into four groups of sheep: fed, NH4Cl acidotic, fasted, and dexamethasone treated. Net and unidirectional plasma glutamine fluxes in the portal-drained viscera (PDV), liver, kidneys, and hindquarters were measured by multiplying venoarterial concentration differences and 14C extraction ratios by the rate of blood flow. In fed sheep, glutamine was released by kidneys and muscle but removed by PDV and liver. In all other sheep, renal glutamine release either decreased or switched over to net removal largely due to increased unidirectional renal utilization. This increased renal glutamine demand was compensated for, during acidosis, by a decreased net hepatic glutamine removal but, during fasting and dexamethasone treatment, by an increased muscle glutamine release. Plasma glutamine and glucose turnover rates averaged 11-12 and 19-24 mmol/h but the percentage of glutamine converted to glucose was higher during fasting and dexamethasone treatment (21%) than in normal fed sheep (17%) perhaps reflecting the increased glutamine removal by the kidneys. Since renal glutamine utilization increases with acidosis and fasting and, since glutamine turnover remains unchanged, glutamine metabolism by other body tissues must be altered to compensate for renal changes.