Subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML) are the major slow virus infections of humans. SSPE is caused by mutant measles virus after long persistence in the brain. Its pathogenesis is discussed, based on accumulating data on molecular properties on measles virus prevalent in the field as well as recent identification of measles virus receptor. Current situation on the therapy of SSPE is also described. PML is caused by the infection of oligodendroglia with persisting JC virus. Its pathogenesis is discussed based on the molecular properties of the archetype and PML type of JC virus, and on the recent findings on the involvement of JC virus T antigen in demyelination. Increase in the incidence of PML in patients with AIDS is discussed in view of the interactions between HIV and JC virus.