DBA/2 CrSlc mice infected with the D variant of encephalomyocarditis virus (EMC-D) (10 PFU/head) developed biphasic hind limb paralysis due to spinal cord lesion. The early phase lesion was characterized by demyelination with infiltration of macrophages in the funiculus lateraris and the late phase lesion by degeneration of motor neurons with infiltration of CD4 + T cells in the cornu ventrale (Takeda et al., Int. J. Exp. Pathol., 1993, 1995. In the present study, treatment with anti-Mac1 monoclonal antibody (MAb) or anti-CD4 MAb prior to virus infection (-3 to -1 days) reduced the early phase lesion and the incidence of the first paralysis. Signals of viral RNAs were observed only in a few oligodendrocytes in the funiculus lateraris. Treatment with anti-CD4 MAb from 31 to 33 days post infection when mice showed recovery from the first paralysis reduced the late phase lesion and prevented the second paralysis. Signals of viral RNAs were still detected in a few degenerated neurons in the cornu ventrale. These results indicate that while macrophages and CD4 + T cells participate in the early phase lesion and paralysis and only CD4 + T cells in the late phase lesion and paralysis. Key words: CD4 + T cells, EMC-D, mouse spinal cord lesion degree of lesion is most prominent in the lumbar spinal cord. The lesion in the early phase is characterized by demyelination associated with infiltration of macrophages in the funiculus lateraris and that in the late phase by degeneration of motor neurons associated with infiltration of CD4 + T cells in the cornu ventrale. The virus titer of the spinal cord peaked at 7 DPI, decreased thereafter, and could no longer be detected even in paralysed mice at 28 DPI. We clarified using an in situ (Received 14 April 2003 / Accepted 6 August 2003 Address corresponding: K. Doi, Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan We first reported that DBA/2 CrSlc mice inoculated with a low dose of the D variant of encephalomyocarditis virus (EMC-D) (10 PFU/head) developed biphasic hind limb paralysis [14]. Briefly, about 60% of the infected mice developed hind limb paralysis by 12 days post infection (DPI), twothirds of them showed recovery by 33 DPI, and 30% of the mice which had shown recovery developed paralysis again by 56 DPI. The character of this disease is biphasic spinal cord lesions. The