Summary. Interleukin-12 is produced by antigen-presenting cells and regulates the balance between TH1/TH2 lymphocyte subsets, promoting cell-mediated immune reactions. Amongst patients with chronic hepatitis B undergoing interferon-alpha treatment, only those who clear hepatitis B virus show a substantial increase in the production of biologically active IL-12 and an inverse ratio between serum levels of IL-12p40 subunit and IL-12. The peak of serum IL-12 occurs after the hepatitis flare and precedes or coincides with the time of HBe seroconversion. These data indicate that IL-12 is an important element for establishing the host immune control on hepatitis B virus replication in patients with chronic hepatitis B virus infection.