A method has been described by which it is possible to estimate the number of particles of vaccine virus which are required to cause infection in the rabbit skin. The method consists essentially in performing a series of intradermal inoculations in rabbits of suitably diluted virus suspensions. The percentage of inoculations at each dilution giving rise to lesions is observed, and the data are subjected to appropriate statistical analysis. Several strains of vaccine virus, differing in their characteristics, have been studied with the following results. Infection with the New York City Board of Health virus appears to follow the injection of a single particle of virus. The same is true for the strain derived from it but cultured in a chick embryo-Tyrode solution medium for a prolonged period. This strain, as has been noted, has largely lost its ability to cause extensive necrosis in the rabbit skin, and causes generalized infection only exceptionally. From the results here reported, it appears that other factors are responsible for the altered character of the lesion than the ability of the virus to establish a foothold in the animal organism. In this respect the cultured appears to be the equal of the original passage virus. Similarly the Noguchi strain of virus is apparently capable of infecting, if a single virus particle is properly introduced.