The effects of herbal medicines that constitute Gam-du-tang and Gung-gui-tang on cytokine-induced cytotoxicity and thyroid major histocompatibility complex (MHC) class II antigen expression in FRTL rat thyrocytes were investigated. No effect on cell growth was found with interferon (IFN)-γ. However, tumor necrosis factor (TNF)-α was cytotoxic, and this was increased by preincubation with IFN-γ. Ethanol extract of Glycyrrhizae Radix, black beans, Angelicae Radix, and Cnidii Rhizoma (0.3—15 mg/ml) in both regimens significantly inhibited IFN-γ and TNF-α-mediated cytotoxicity of rat thyroid cells (p<0.05, p<0.01). In addition, IFN-γ (1—100 U/ml) treatment induced class II antigen expression in up to 60% of FRTL cells, as detected by a murine monoclonal antibody to rat MHC class II antigen (FITC-OX6). Aberrant thyroid cell MHC class II antigen expression induced by IFN-γ is suppressed by the extract of herbal medicines. These results indicate that herbal medicines inhibit cytokine-induced thyroid cell destruction, therefore, may have therapeutic potential in the treatment of autoimmune thyroid disease.