This study investigates T cell-dependent experimental liver injury in mice induced by concanavalin A (Con A). Male NMRI or BALB/c mice developed severe liver injury, as indicated by transaminase release, within 8 hours after receiving an intravenous dose of >1.5 mg/kg Con A. Histopathologically, only the liver was affected, with leukocyte sticking to endothelial cells and hepatocyte bleb formation observed under electron microscopy. The hepatotoxicity of Con A was not correlated with its agglutination activity or sugar specificity. Dexamethasone, cyclosporine A, and FK 506 protected mice, while indomethacin did not. Con A-induced hepatitis was associated with increased serum IL-2 levels. Mice with severe combined immunodeficiency (SCID) or athymic nude mice were resistant, suggesting T lymphocytes were involved. Pretreatment with anti-T lymphocyte antibodies or anti-CD4 monoclonal antibodies protected mice, while anti-CD8 did not. Silica particle pretreatment, which depletes macrophages, also prevented Con A-induced hepatitis. These findings indicate that Con A-induced liver injury depends on T lymphocyte activation by macrophages in the presence of Con A. The model may be useful for studying immunologically mediated hepatic disorders such as autoimmune chronic active hepatitis. The study also shows that Con A-induced liver injury involves macrophage-T helper cell interactions, with IL-2 release playing a key role. The results suggest that T helper cell activation is a critical step in the pathogenesis of Con A-induced hepatitis. The model provides a valuable tool for studying the pathophysiology of autoimmune diseases.This study investigates T cell-dependent experimental liver injury in mice induced by concanavalin A (Con A). Male NMRI or BALB/c mice developed severe liver injury, as indicated by transaminase release, within 8 hours after receiving an intravenous dose of >1.5 mg/kg Con A. Histopathologically, only the liver was affected, with leukocyte sticking to endothelial cells and hepatocyte bleb formation observed under electron microscopy. The hepatotoxicity of Con A was not correlated with its agglutination activity or sugar specificity. Dexamethasone, cyclosporine A, and FK 506 protected mice, while indomethacin did not. Con A-induced hepatitis was associated with increased serum IL-2 levels. Mice with severe combined immunodeficiency (SCID) or athymic nude mice were resistant, suggesting T lymphocytes were involved. Pretreatment with anti-T lymphocyte antibodies or anti-CD4 monoclonal antibodies protected mice, while anti-CD8 did not. Silica particle pretreatment, which depletes macrophages, also prevented Con A-induced hepatitis. These findings indicate that Con A-induced liver injury depends on T lymphocyte activation by macrophages in the presence of Con A. The model may be useful for studying immunologically mediated hepatic disorders such as autoimmune chronic active hepatitis. The study also shows that Con A-induced liver injury involves macrophage-T helper cell interactions, with IL-2 release playing a key role. The results suggest that T helper cell activation is a critical step in the pathogenesis of Con A-induced hepatitis. The model provides a valuable tool for studying the pathophysiology of autoimmune diseases.