In situ hybridization and PCR studies have demonstrated that enteroviruses of the human picornavividae, and in particular coxsackieviruses of group B (CVB), are detectable in endomyocardial biopsies of patients with acute and chronic myocarditis, indicating the possibility of enterovirus persistence in the human heart. As well, such infections are observed in patients with end-stage dilated cardiomyopathy, suggesting an etiologic link between myocarditis and dilated cardiomyopathy. The molecular diagnosis of persistent heart muscle infection allows to differentiate myocarditis and dilated cardiomyopathy, sustained by virus persistence, from postviral immune-mediated cardiac disease. Apart from providing an etiologic diagnosis, there are therapeutic implications from in situ demonstration of myocardial enterovirus infection. As to whether antiviral therapy with interferon is capable of providing protection against enterovirus myocarditis must be determined by controlled prospective clinical studies. Immunosuppressive therapy of myocarditis appears to be justified only after exclusion of persistent heart muscle infection. Experimental studies indicate that altered viral replication strategies, the incompetence of effector mediators of local immunity to eliminate persistently infected myocardial cells as well as infection of cellular constituents of the immune system itself, are major pathogenic determinants for development and maintenance of chronic myocarditis and cardiomyopathy.