We have developed two models of myocarditis in mice. The first is produced by infection with Coxsackievirus B3; the second results from immunization with cardiac myosin. Both forms of myocarditis occur in the same genetically predisposed strains. Genetically resistant mice can be rendered susceptible to myocarditis by co-treatment with cytokines IL-1 or TNF. Moreover, the disease is inhibited by administration of an antagonist of IL-1. These models will be useful for clarifying outstanding issues related to human myocarditis or dilated cardiomyopathy.