The present report demonstrated the following: a) hypertyraminemia of dogs with portacaval shunt was caused by both an increased systemic bioavailability of oral tyramine and decreased metabolism of tyramine by monoamine oxidase enzyme. b) Shunted dogs had significant depletion in dopamine and norepinephrine in various sections of the brain. This was followed by a concommitant increase in tyrosine and tyramine. c) The degree of these metabolic abnormalities (a,b) correlated significantly with the determination of the physical and mental status of these dogs. These findings are of clinical importance since hypertyraminemia is a serious metabolic abnormality encountered in patients with liver disease. In the case of Reye's syndrome, plasma tyramine was substantially raised and the degree of hypertyraminemia correlated significantly with duration and stage of coma in these patients as well as with concentrations of its precursor, the amino acid, tyrosine. Furthermore, the depletion in brain (hypothalamus, corpus striatum, etc) catecholamines and their subsequent elevation in CSF of shunted dogs closely resembles our recent findings in patients with Reye's syndrome. In four of these patients with stage III coma or deeper, ventricular fluid dopamine and norepinephirne was substantially higher than in other hospital patients without encephalopathy. Moreover, these patients also demonstrated significant increases in serum prolactin. This may represent an indirect evidence that encephalopathy of Reye's syndrome may be related to hypothalamic dopamine depletion. Therefore dogs with portacaval shunt represent an appropriate model for studying changes in tyrosine, tyramine and catecholamines metabolism seen in different categories of liver disease.