From the comparative studies of the virulence of several vaccinia virus strains by intrathalamic inoculation into cynomolgus monkeys, the following results were observed. The CV1 virus was most virulent, the New York City Board of Health, Ikeda, EM63, and Lister viruses were slightly less virulent, and DIs and LC16 viruses least virulent. The characteristic findings were widespread inflammatory lesions in the meninges and choroid plexus which were closely associated with the replication of vaccinia virus, and parenchymal lesions which might be referred to a encephalopathy in the deceased monkeys. Meningoencephalitis was, however, ofter recognized in the monkeys sacrificed at 14 days postinoculation and those dying late.