Objective: To study antibody dependent cell-mediated cytotoxicity (ADCC) on hepatocytes during immune response in halothane hepatitis of guinea pigs. Methods: The model of halothane hepatitis of guinea pigs was used. Mixed lymphocyte hepatocytes were cultured and supernatants containing specific antigens and cytokines were added. The changes of hepatic function in immune response of halothane hepatitis were analyzed. Results: The cytotoxicity on hepatocytes induced by halothane 3 times included ADCC mediated by specific antigens. ADCC on hepatocytes induced by halothane once required the second induction. There was no cytotoxicity on hepatocytes of specific antigens and cytokines produced by proliferative lymphocytes induced by Kupffer cells. Conclusion: Humoral immunity is mainly ADCC. Specific antibodies and cytokines can not separately kill hepatocytes. The extent of immune response is related to induction by halothane.