As experience with penicillin in the treatment of venereal syphilis has grown over the last decade, this drug, used without adjuvants, has become increasingly widely accepted as being effective, convenient, non-toxic, and relatively inexpensive. Metal chemotherapy required the use of repeated subcurative doses over a long period of time and was essentially suppressive in character; penicillin can be given in the form of repository preparations which ensure a treponemacidal blood-level of long duration. These can be given in large single doses or in repeated smaller doses; the therapeutic results will not vary whichever of these procedures is used.In the first part of this paper, the authors discuss the effect of penicillin and the time factor, the choice of penicillin preparation, the mode of administration, and the reaction to infection with Treponema pallidum. In the second part, they consider the present status of penicillin therapy in venereal syphilis, dealing with the principles of follow-up and control; with the treatment of early, latent, late, and congenital syphilis; and with the treatment of incubating syphilis and contacts.