Alterations in tyrosine metabolism associated with portacaval shunt in experimental animals and with human hepatic cirrhosis confirm earlier observations suggesting disturbance of tyrosine metabolism in conditions associated with liver failure. Diversion of portal blood from the liver by portacaval shunt resulted in early and prolonged increased activity of hepatic tyrosine-α-ketoglutarate transaminase (tyrosine transaminase) in normal rat or canine liver. The increased enzyme activity could be blocked by administration of dactinomycin (actinomycin D) suggesting postshunt hepatic synthesis of tyrosine transaminase. The mechanism of enzyme synthesis may be related to hormonal alterations caused by the portacaval shunt or to postshunt changes in amino acid or glucose concentrations in the liver. Alterations in tissue levels of free tyrosine occurred after portacaval shunt. Decreased average levels of tyrosine transaminase enzyme activity were observed in human alcoholic and posthepatitic cirrhosis.