Suckling mice readily succumb to infection with small doses of many strains of vaccinia virus, but lethal vaccinial infection in mature mice can be established only with certain virus strains in appropriate doses and by certain routes of inoculation, and only in mice of certain genotypes (1,2). Lethal infection against which mice can be immunized, can be established by the respiratory route after intranasal inoculation(3). Infections established by this route, which have been used in studying antiviral drugs, would be useful in assaying the protective potency of inactivated vaccines. The infection is less unnatural than intracranial inoculation with neurovaccinia strains and possibly simulates the natural mode of infection in smallpox.(4) The strains of vaccinia virus used (Table 1) were obtained from the following sources: lister—standard vaccine strain Elstree; levaditi—dried rabbit testicular passage Elstree (1939); copenhagen—glycerolated calf lymph Utrecht (1961); tashkent—dried vaccine strain Moscow (1962). The mouse neurotropic strains wr and ihd were obtained as dried infected mouse brain through the courtesy of Drs Kingsley Sanders and D. J. Bauer in 1955 and 1966 respectively.