Serum amino acid concentrations in cirrhotic patients with and without hepatocellular carcinoma (HCC) were investigated. Elevation of serum aromatic amino acids (AAA) and methionine levels observed in cirrhotic patients without malignancy was not apparent in cirrhotic cases with HCC, and thus the ratio of branched chain amino acids (BCAA) to AAA was not so diminished in the latter cases. Development of hepatic encephalopathy in cirrhotic patients with HCC led to only a slight change in the serum aminogram characteristic of hepatic failure. In patients who underwent operations, tissue amino acid compositions of hepatocellular, gastric, and colon cancers were compared with each other and their respective surrounding epithelia. Amino acid contents in the tumor tissue were generally higher than those in the respective nontumorous parts, especially in the case of HCC. The methionine, tyrosine, and phenylalanine contents in HCC were much higher than in cirrhotic or normal liver. Serum aminograms in rats with ethionine-induced HCC were similar to those in cirrhotic patients with HCC. Amino acid contents in HCC were much higher than those in the surrounding cirrhotic liver tissue of rats. Serum and liver tyrosine and isoleucine contents rose significantly in rats 5 to 6 weeks after the initiation of a 0.25% ethionine-containing diet. After the 20th week of the experiment, by which time well-differentiated HCC had developed, liver tyrosine and isoleucine contents increased whereas serum isoleucine concentrations decreased. The results suggest that the serum amino acid patterns characteristic of cirrhotic patients with HCC may result from the increased consumption of amino acids by HCC. Determinations of the amino acid levels are also useful for estimating the prognosis and discovering imminent hepatic encephalopathy in cirrhotic patients with HCC.