Angiogenesis is of vital importance during the development and progression of solid tumors. To examine the role of vascular endothelial growth factor (VEGF) in hepatocarcinogenesis, we evaluated the expression of peptide in normal human liver (n = 6) and in 36 cases of hepatocellular carcinoma (HCC). Immunoreactivity for VEGF was present in the extracellular matrix of the portal tracts in the normal and nontumor part of liver, but not in hepatocytes and bile duct epithelium. For HCC, variable amounts of VEGF were expressed in 13 cases (36.1%) of tumor cells. Using a logistic regression model, expression of VEGF was significantly associated with a higher proliferative index (P = .01) and sonographic portal vein thrombosis (P = .05). However, VEGF expression did not correlate with a biochemical liver profile, alpha-fetoprotein levels, histological grading, gender, or clinical stage of cirrhosis (P > 0.1, respectively). Log-rank test showed that evaluation of VEGF did not provide more prognostic information (P > .5) than that from tumor volume and portal vein thrombosis (P < .01, respectively). In addition, VEGF was always present in the fibrovascular stroma or pericellular matrix of HCC, although no strong relationship was observed with the expression of VEGF in tumor cells (P > .5). Our data suggested that expression of VEGF may characterize a progression toward higher proliferation in hepatocarcinogenesis in vivo. The relevance of VEGF existing in the extracellular matrix of the normal liver and HCC remains to be clarified.