Studies were undertaken to evaluate the role of interleukin 6 (IL-6) in the pathogenesis of chronic hepatitis B. Using recently developed sensitive and specific enzyme-linked immunosorbent assay, we determined serum levels of IL-6 in patients with chronic active hepatitis B (B-CAH), chronic persistent hepatitis B (B-CPH), and primary biliary cirrhosis (PBC). Serum IL-6 activity tended to increase in patients with B-CAH (38.4 +/- 68.0 pg/ml) (+/- SD), compared with controls (9.7 +/- 6.8 pg/ml), although the difference was not significant because of the wide scatter in values. IL-6 levels in B-CPH and PBC were similar to those of controls. There was a significant correlation between the levels of IL-6 and aminotransferase in B-CAH. In addition, IL-6 activity was significantly enhanced during acute exacerbation of the illness, accompanied by clearance of HBeAg. Patients who received IFN-alpha and IL-2 therapy showed depressed IL-6 activity during treatment, and a rebound beyond pretreatment values after cessation of therapy. These findings suggest that IL-6 plays a role in the development of chronic hepatitis B, and it may contribute, at least in part, to the elimination of HB virus.