Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been examined in 38 patients with chronic hepatitis C liver disease treated with interferon. The sICAM-1 values were found to correlate significantly with the ALT values. Pre-treatment sICAM-1 values of responder and nonresponder patients were not significantly different while, by the end of the treatment, the values of responders were significantly lower compared to those of nonresponders. However, no difference could be found between sustained and relapse responders. Of the 21 patients examined for PBMC HCV-RNA, 15 (71.4%) were found to be positive. Neither the rate of responsivity to interferon treatment, nor the mean sICAM-1 values correlated with the positivity of PBMC HCV-RNA. However, the clearance of serum and PBMC HCV-RNA was associated to a significant decrease of sICAM-1 and ALT levels. In conclusion, sICAM-1 values were found to correlate with ongoing viral replication and liver cytonecrosis, but were not influenced by the concomitant HCV infection of PBMC.