Giant cell myocarditis is a rare disorder characterized by the histologic hallmark of diffuse inflammatory infiltrates with the appearance of multinucleated giant cells. We report on a 52-year-old man who died of rapidly progressive cardiogenic shock due to giant cell myocarditis. Serological and immunoblotting techniques revealed a myocardial infection with coxsackie B2 virus, suggesting a viral etiology of this disease. Here we present evidence for the involvement of autoimmune responses to the myocardium as numerous cardiomyocytes exhibited deposits of cell-adherent immunoglobulins. Although other causative factors may initiate giant cell myocarditis as well, our case suggests coxsackie B2 virus as one etiologic agent capable of triggering autoimmune reactions to altered heart tissue.