Molecular hybridization studies have demonstrated that human enteroviruses, including group B coxsackieviruses (CVB), are detectable not only in endomyocardial biopsies of patients with acute enterovirus myocarditis but also in those with chronic disease. Such infections are observed in some patients with end-stage dilated cardiomyopathy, indicating the possibility of persistent heart muscle infection. Enterovirus persistence in the human heart is supported by the recent discovery in various murine models of enterovirus myocarditis that chronic inflamed heart muscle lesions are consistently associated with enterovirus persistence. Application of in-situ hybridization in a multiorgan study of CVB3-infected immunocompetent mice now reveals that, in addition to the myocardium, spleen and lymph nodes are persistently infected. During acute myocarditis, the majority of infected spleen cells was found to be located within the follicles of spleen and lymph nodes. At later stages of the disease, enteroviral infection was shown to be restricted to cells of the germinal centre in secondary follicles of spleen and lymph nodes. Thus, infected immunocompetent cells may play an important role in dissemination of the virus in the host and maintenance of a non-cardiac viral reservoir.