Fumonisin B₁ (FB₁) is a common mycotoxin from Fusarium verticillioides that infests corn and other cereals.  Fumonisin hepatotoxicity in mice was reduced in animals lacking TNFα receptor I or II, and also in mice after the deletion of interferon γ, another cytokine inducing TNFα.  However, after deletion of TNFα itself or both TNFα receptors, hepatotoxicity increased following FB1 treatment.  Mice carrying human TNFα transgene were also resistant to FB₁ hepatotoxicity.  Targeted deletion of interleukin-12, another inflammatory cytokine that is induced in liver after FB₁ exposure and also regulates the production of TNFα, was unable to modify the hepatotoxic response to the mycotoxin.  The hepatotoxicity in mice in response to FB1 was abolished after pretreating animals with antibody against Thy-1.2 (a surface antigen of mature lymphocytes) but not in nude mice or in mice after deletion of NK cells, T cell receptor α or CD8a.  Similarly, intervening effects of TNFα by pharmacological antagonists and anti-TNFα antibody provided paradoxical responses suggesting dual role of this cytokine both in cell survival and toxicity.  Use of genetically modified mice therefore has provided valuable information; unexpected responses in some instances were explained by reestablishment of the constitutive expression of other apoptotic or antiapoptotic factors in livers of modified animals.  Localized hepatic immune responses in mice are important regulators of the toxic outcome after FB₁ treatment.