Summary Virological, immunological and pathological data were obtained from a child who died at the age of 13 1/2 yr? following an illness of 33 months. Her fatal illness may be related to infection by the vaccinia virus administered as a primary vaccination against smallpox at the age of seven months. Antibody titers against vaccinia virus of 1:5000 were found in her serum and several spinal fluid determinations revealed antibody titers from 1:16 to 1:64 when tested by the vaccinia neutralization test with and without complement. Rabbits inoculated with brain material plus adjuvant developed titers against vaccinia virus. Control animals were negative. The patient had a severe form of subacute disseminated encephalomyelitis with necrosis and cavity formation, characterized by perivascular infiltration, circumscribed and diffuse sclerosis. We are indebted to Alice Kolangian and Natalie Stein for technical assistance. We thank C. Henry Kempe and Kenneth McIntosh for performing the vaccinia neutralization tests. James N. Miller kindly provided sera from control rabbits.