Patterns of seven key carbohydrate-metabolizing enzyme activities were examined in liver tissue from 125 patients with various liver diseases. Along with the progression of chronic hepatitis to liver cirrhosis (LC), activities of high-Km hexokinase (high-Km HK), fructose-1, 6-bisphosphatase (FBPase) and glucose 6-phosphatase (G6Pase) decreased, and those of glucose 6-phosphate dehydrogenase (G6PD) and hexokinase (HK) increased. In hepatocellular carcinoma (HCC), similar alterations of these enzyme activities were observed. The extent of enzyme alteration was greatest in HCC and fetal liver, and slightly less in LC and the icteric stage of acute hepatitis. Phosphofructokinase (PFK) activity was increased in acute hepatitis, and pyruvate kinase (PK) activity was increased in HCC. Principal component analysis showed G6PD and HK to be located close to α-fetoprotein and the GOT/GPT ratio. G6Pase and FBPase were distributed symmetrically to G6PD and HK. Thus, the factor loadings effectively separated HCC from the benign liver diseases. The results indicate that the determinations of these enzyme activities are useful in the clinical assessment of the progression of liver disease, which is not revealed by routine blood chemistry.