The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and Nacetyl-L-tyrosine (Nac-Tyrf were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Clto,) of Ala-Tyr was higher than of Gly-Tyr (3,169 t 214 vs. 1,780 r 199 dJkg/min, P < .Ol), and both exceeded clearance of Nac-Tyr (309 t 29 mlflrglmin, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 i 26 mUkg/ min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cl,, of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 5 38.4 vs. 484.4 5 41.4 mWkg/min, P < .001) and half-life (k,,) was retarded from 14.4 2 1.4 to 90.2 ? 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac-Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala-Tyr, for the first time, enables a simple rapid nonisotope evalution of tyrosine kinetics for assessement of liver function. (HEPATOLOGY 1995;21:923-928.