Male 8 to 20-week-old NMRI mice (an outbred strain) infected with the encephalomyocarditis virus (EMCV) plaque variant (PV) 7 consistently develop a distinct myocarditis with a relatively low mortality (21%). Myocarditis occurs in essence independent of the virus dose applied, and other internal organs are not affected. Nevertheless, 3.5-week-old NMRI mice perished within 5 days of virus inoculation and exhibited disseminated myofibrillar degeneration (MFD); this obviously virus-induced myocardial damage was accompanied by scanty inflammatory infiltrates. EMCV PV7 infection of adult male C57Bl/6 and DBA/2 mice causes myocarditis comparable to that seen in NMRI mice. In DBA/2 mice, however, the virus-induced myocardial necrosis is complicated by subtotal calcification. This strain has a genetically determined "spontaneous" calcification of the myocardium, as shown by the study of uninfected controls. EMCV PV7-infected NMRI mice appear a promising model for study of long-term effects of viral myocarditis, possibly including cardiomyopathy. Furthermore, this outbred mouse strain offers the possibility of examining the pathogenesis of direct viral cytolysis and its relation to MFD as well as immunologically mediated cell damage.