The interrelationships of [14C] glutamine metabolism and urea production were studied in the isolated perfused rat liver. Whereas urea formation remained linear throughout the perfusion period there was continuous utilisation and production of glutamine maintaining its concentration in the perfusate within the physiological range for rat plasma. Chronic NH4Cl induced metabolic acidosis did not effect either the production of urea or the turnover of glutamine, in marked contrast to findings in the whole animal.