Pooled serum from hamsters immune to syphilitic infection conferred complete protection on recipient hamsters challenged with Treponema pallidum subsp. endemicum. Cutaneous lesions did not develop, and the recipients' lymph nodes weighed less than those of controls and contained no treponemes. Treponemicidal activity in the pooled immune serum was relatively high. When treponemes were incubated in immune serum and complement and the suspension was then inoculated into hamsters, recipients developed neither lesions nor enlarged lymph nodes teeming with treponemes. With hamsters already infected for several weeks, however, immune serum failed to impair or influence the progression of syphilis. Treponemes were eliminated only when immune serum was administered within a short time of syphilitic infection. These results demonstrate that hamsters develop an effective serum-mediated treponemicidal response, but this response is not sufficient to eliminate treponemes at the primary foci of infection.