Valvular tissue from a patient with possible Coxsackie B<sub>4</sub> virus infection was studied. Antigen to Coxsackie B<sub>4</sub> virus was detected in cells of the mitral valve by immunofluorescent staining. Histologic examination of the mitral valve revealed widespread increase in collagenous fibers, subendocardial edema and infiltration of basophilic cells, formation of verruca on the mitral valve surface, and fibrinoid degeneration of collagen fibers. Fragmented fibroblasts and numerous fibers of elastin were observed electron microscopically. The pathologic changes were similar to lesions of endocarditis in rheumatic fever. This case reveals the possible role of viruses in production of valvular heart disease in man usually attributed to rheumatic fever due to streptococcal infections.