Evidence of a role for human factor(s) in immunity to experimental syphilis has been provided by the demonstration that passive immunization of rabbits by daily i.v. injections of immune serum significantly delays the appearance and markedly diminishes the severity and duration of lesions which develop after challenge with Treponema pallidum. Five rabbits were injected daily over 37 days with 3 ml/kg body weight of pooled immune rabbit serum injection with 1.1 X 10(3) T. pallidum, Nichols strain, at each of four sites. The animals developed atypical lesions of short duration after an average delay in onset of 28 days short duration after an average delay in onset of 28 days beyond the development of typical lesions in control animals similarly injected with nonimmune serum or saline. The failure of passive immunization to provide complete protection was evident not only in the development of the atypical lesions, but also in the demonstration of disseminated infection in the tissues of three of the four surviving animals 7 months after challenge. The possibility that incomplete protection may have been due to 1) insufficient immune serum levels, 2) intracellular location of T. pallidum, and/or 3) cell-mediated mechanisms is discussed.