1. The possible involvement of renal glutamine synthesis in the regulation of ammoniagenesis during metabolic acidosis has been investigated.
2. Using an isotope dilution technique glutamine synthesis has been demonstrated in the intact perfused rat kidney, despite zero net balance for glutamine in this preparation.
3. Inhibition of glutamine synthesis resulted in increased ammonia production in isolated cortical tubules. The rates of these processes were comparable.
4. We conclude that recycling of nitrogen through glutamine synthesis and glutamine hydrolysis could play a quantitatively significant role in the control of ammonia excretion by the kidney, particularly in acute acidosis where the fall in pH seems to inhibit glutamine synthesis.