The pathogenesis of acute canine distemper in three naturally infected dogs was investigated. The lymphoid organs showed atrophy without secondary follicles. The distribution of canine distemper virus (CDV) antigens was examined immunohistochemically with monoclonal antibodies specific for canine Thy-1, immunoglobulin (Ig) M, CD4, CD8, CD21 and CD45RB, and anti-measles virus nucleocapsid protein serum. The viral antigens were located in the T-cell-dependent areas and in the follicles of lymphoid organs; they were observed mainly in the Thy-1, or CD4-positive cells, but also in the CD8-, CD21-, or IgM-positive cells. The results indicated that Thy-1-positive and CD4-positive T cells serve as major target cells for CDV during the acute stage of infection.