This study reports the increase of immunoregulatory T helper cell type 1 response and elimination of HBV-DNA during IL-12 therapy in a patient with chronic hepatitis B virus infection who had not responded to three previous interferon-alpha therapies and one treatment with Famciclovir over a period of 6 years. The patient received IL-12 at a dose of 0.5 microgram/kg bodyweight weekly. Peripheral blood mononuclear cells were isolated before and during IL-12 application and incubated for 7 days with specific type 1 (purified protein derivative) and type 2 (tetanus-toxoid) TH cell antigens as well as with a macrophage/monocyte activating antigen (Bacille Calmette-Guérin). In the supernatants cytokines were determined by a double-sandwich ELISA. After 8 weeks HBV-DNA became negative and HBeAg seroconversion to anti-HBeAg occurred. Immunologically the loss of viremia was accompanied by a strong increase of the purified protein derivative-induced production of the type 1 cytokine interferon-gamma (1219 pg/mL before, 13,138 pg/mL after IL-12 therapy). Furthermore, Bacille Calmette-Guérin-induced secretion of the macrophage/monocyte-associated cytokines IL-1, tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor was higher at the end of therapy. This case indicates that IL-12 enhances type 1 T helper cell activity which may be a predisposition for elimination of HBeAg and successful treatment of hepatitis B.