Abstract A 2-fold increase in the activity of hepatic glutamine synthetase ( L -glutamate: ammonia ligase (ADP), EC 6.3.1.2) was observed following the administration of cortisol to adrenalectomized rats and this response was prevented by actinomycin D. The enzyme showed a marked decrease in activity in the liver of rats following adrenalectomy and in intact rats which were fed a high protien diet for 1 week or starved for 24 h. The growth of transplantable tumors lowered the activity of this enzyme in liver but did not significantly influence its induction by cortisol. Feeding 3′-methyl-4-dimethylaminoazobenzene (0.06% in the diet) for 3 months reduced the hepatic activity of this enzyme to 40% of the normal value, and the resultant hepatomas had barely detectable activity of this enzyme.