We investigated polyamine metabolism in hepatocellular carcinoma (HCC) with respect to tumor volume doubling time, degree of differentiation, and prevalence of portal invasion and intrahepatic metastasis. Ornithine decarboxylase (ODC) activity and the spermidine/spermine ratio were correlated with tumor volume doubling time. ODC activity was higher in moderately and poorly differentiated HCC than in well-differentiated HCC. The prevalence of portal invasion and intrehapatic metastasis was higher in patients with high ODC activities. We conclude that polyamine metabolism in HCC estimates the degree of malignancy.