Serum levels of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were measured in 38 patients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 43 with hepatocellular carcinoma (HCC) using enzyme-linked immunosorbent assays. All the patients showed significantly higher serum levels of these circulating adhesion molecules than 40 normal controls. The serum E-selectin level showed no relationship to the levels of the other adhesion molecules. Serum VCAM-1 levels were well correlated with serum ICAM-1 levels in CH and LC patients. In HCC patients, however, the close correlation between VCAM-1 and ICAM-1 was lost, because the patients with large tumors (100 cm2) showed relatively high ICAM-1 levels. The amount of ICAM-1 shed from the tumor cells was calculated in the HCC patients as follows: actual serum ICAM-1 level minus basal ICAM-1 level released from the noncancerous liver (obtained from the regression line between ICAM-1 and VCAM-1 in CH and LC patients). Although there was no relationship between the actual ICAM-1 level and the tumor size in HCC patients, the predicted ICAM-1 shedding was closely correlated with tumor size. When in situ expression of these adhesion molecules was evaluated in 10 HCC tissues using immunohistochemistry, the tumor cells exhibited enhanced ICAM-1 expression but did not express E-selectin and VCAM-1. These results suggest that the elevated serum levels of adhesion molecules in HCC patients are mainly attributable to the associated liver inflammation, although some ICAM-1 is shed into the circulation by tumor cells.