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When penicillin is added to a suspension of spirochetes (S. pa/1/da, Reiter), the number of viable organisms has been shown to fall off at a rate which is largely independent of the number of organisms, and which varies with the concentration of penicillin in the range 0.01 to 1 unit per cc. (1). If the ini6al number of organisms is increased, a larger proportion must be killed in order to prevent growth in subculture. It is clear that the penicillin must then be allowed to act for a longer period of time, or, the time factor remaining constant, the concentration of penicillin must be increased, within the range which affects the rate of its spirocheticidal action.These elementary considerations probably apply to most organisms which are susceptible to penicillin in titro. To a certain extent they are probably also valid in ~ivo. With acute bacterial infections, the longer one waits before administering penicillln~ the more organisms must be killed in order to effect cure, and the more effectively must the penicillin be administered, either by giving more injections, or by increasing the size d the individual dose. By the same token, in experimental infections, if the size of the inoculum is progressively increased, more penicillin should be necessary for cure.As will be shown in the present paper, precisely these relationships have been found to obtain in experimental syphilis. If rabbits are inocuhted with varying numbers of organisms, there is a corresponding variation in the amount of penicillin necessary to abort the infection when administered 4 days after inoculation. Conversely, if the size of the inoculum is fixed, and if the animals are treated at varying intervals after their inoculation, there is a progressive increase in the amount of penicillin necessary to abort the infection, presumably because of the interim multiplication of spirochetes in vivo.The conditions which most favor the drug are therefore a small inoculum and treatment during the incubation period, before the organisms have multiplied to a significant degree. Under such circumstances, extraordinarily small doses of penicillin suffice to abort syphilitic infection in rabbits. Even with inocula probably greater than those operative in the natural infection, the 423 on

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