Serum levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured in 23 patients with chronic hepatitis (CH), 22 with liver cirrhosis (LC) and 45 with hepatocellular carcinoma (HCC) using an ELISA. Serum samples from all patients showed significantly higher cICAM-1 levels than serum from 50 normal controls. The cICAM-1 level was significantly increased in LC or HCC when compared with CH, but no differences were noted between LC and HCC. Levels of cICAM-1 correlated well with serum bilirubin, retention rate of indocyanine green, hyaluronic acid, type IV collagen 7-S and type III procollagen peptide levels but not with tumor size or circulating tumor markers (alpha-fetoprotein and des-gamma-carboxyprothrombin). Our findings indicate that the measurement of cICAM-1 is useful for the determination of the severity of liver disease and hepatic fibrosis. HCC tissues obtained from 10 patients were immunohistochemically stained for ICAM-1. Enhanced ICAM-1 expression was found on the tumor cell membranes. Sequential measurements of cICAM-1 levels showed that they changed in a similar manner to those of alpha-fetoprotein during the course of treatment of HCC in a patient with very high pretreatment levels of both markers. These results suggest that HCC cells shed ICAM-1 into the circulation. We conclude that cICAM-1 is not a diagnostic marker for HCC, but may be useful for monitoring the response to treatment.