The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors (gamma delta) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3). The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice. The survival days of mice, and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined. The proportions of gamma delta T cells in blood, spleen and liver, and cytokines secreted by hepatic gamma delta T cells were analyzed by flow cytometry. The function of hepatic gamma delta T cells was examined by cytotoxicity assay. Balb/cJ mice died in 3 to 6 days post MHV-3 infection, with severe hepatic necrosis and significant augmentation of serum ALT and AST levels. The proportions of gamma delta T cells in blood, spleen and liver were significantly increased post MHV-3 infection, while those of the early activating molecule CD69-expressing gamma delta T cells and productions of cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) increased remarkably in the liver. These highly activated liver gamma delta T cells were cytotoxic to MHV-3-infected hepatocytes in vitro and this effect of liver gamma delta T cells against hepatocytes might involve the TNF-alpha and IFN-gamma pathway. These results demonstrated that gamma delta T cells might contribute to the pathogenesis of MHV-3-induced FVH through the effector cytokines TNF-alpha and IFN-gamma.