IFN-alpha represents the treatment of choice in chronic hepatitis C. It acts directly on the cells infected by the virus and indirectly via the cytokine network. We studied the behavior of interleukin 6 (IL-6), a cytokine that is particularly active in the liver and considered an index of liver inflammation and necrosis, in order to evaluate the relationships between IFN-alpha administration and serum levels of this cytokine. Our study series was composed of 60 patients (32 males, 28 females, mean age 53.03 +/- 12.7 years) affected by chronic hepatitis C and 24 healthy controls (14 males, 13 females, mean age 45.8 +/- 5.9 years). We determined serum IL-6 concentrations before and after 3,000,000 IU of IFN-alpha t.i.w./6 months in the former and compared them with levels observed in the controls. Pre- and post-treatment serum IL-6 levels were higher in chronic hepatitis patients and correlated with HAI score and HCV RNA prior to treatment. Diversely, this correlation was less significant after completion of the treatment. Furthermore, IL-6 concentrations depended on the type of response to treatment, i.e. they decreased in complete responders, while increased in partial and non-responders. Our data indicate that IL-6 concentrations, before treatment, are expression of viral-induced inflammation and that, after treatment, may be increased by the action of IFN-alpha treatment.