Herpes simplex virus types 1 and 2 induced acute and chronic cardiac damage in suckling and weaning mice after intranasal inoculation. Signs of virus replication were detected by light, immunofluorescent, and electron microscopy techniques. Virtually all of the cardiac tissues appeared to be susceptible to herpes simplex virus. The myocardium, however, was most regularly affected. The viral lesions were discrete during the acute phase of infection. The cardiac damage, however, was more extensive in some of the chronically infected mice. Morphologically, these lesions either resembled the acute ones or were associated with inflammatory granulomatous and sclerotic changes.