Intercellular adhesion molecule 1 (ICAM-1) is a marker of inflammation and tissue damage. Levels of soluble ICAM-1 (sICAM-1) were measured in 71 patients with chronic C hepatitis treated with interferon (IFN)-alpha-2a, at baseline and at every 3 months of therapy, and in 42 normal control subjects. The levels of sICAM-1 were significantly higher in the patient than in the control subject group, particularly among cirrhotics. Baseline sICAM-1 levels were similar in responders and nonresponders. By contrast, the concentration of sICAM-1 decreased significantly only in responders during the first 3 months of therapy. The probability of response to treatment, analyzed by Kaplan-Meier analysis, was much higher in the group showing a decrease of sICAM-1 than in the patients who did not show such a decrease. In conclusion, a "longitudinal" evaluation of serum levels of sICAM-1 in the first period of treatment is particularly useful in the identification of patients with high significant probability of response to treatment.