BALB/c mice infected with 10(5) pfu of the D variant of encephalomyocarditis virus were examined histopathologically during the subacute stage of infection. Main pathologic changes were observed in the brain, heart (massive myocardial necrosis with subsequent organization (i.e., replacement of necrotic myocardium by connective tissue) and congestion and dilatation of the right ventricle) and pancreas (moderate degranulation of beta-cells resulting in elevation of blood glucose level). The brain lesions were found most frequently in the pyramidal layer of the hippocampus and the granular layer of the cerebellum and were characterized by degeneration of neurons containing virus antigens. Perivascular mononuclear cell infiltration, spreading to the adjacent brain tissue, and thrombosis in small vessels were also frequently seen. Focal loss of neurons and gliosis developed later in these lesions.