Background & Aims: The kidney plays an important role in ammonia metabolism. In this study, we studied the hypothesis that the kidney can acutely diminish ammonia release after portacaval shunting. Methods: Thirteen patients with cirrhosis (6F/7M, age 54.4 (±3.3) yrs) were studied. Blood was sampled prior to and one hour after transjugular intrahepatic stent shunt (TIPSS) insertion from the portal vein, a hepatic vein, the right renal vein and the femoral vein and renal and liver plasma flow were measured. Results: Prior to TIPSS, renal ammonia release was significantly higher than ammonia release from the splanchnic region, which was not significantly different from zero. TIPSS insertion did not change arterial ammonia concentration or ammonia release from the splanchnic region, but reduced renal ammonia release into the circulation (p<0.05) to values that were not different from zero. TIPSS resulted in a tendency towards increased venous minus arterial ammonia concentration differences across leg muscle. Post-TIPSS ammonia efflux via portasystemic shunts was estimated to be 7 times higher than renal efflux. Conclusions: Kidneys have the ability to acutely diminish systemic ammonia release after portacaval shunting. Diminished renal ammonia release and enhanced muscle ammonia uptake are important mechanisms by which the cirrhotic patient maintains ammonia homeostasis after portasystemic shunting.