The persistence or loss of IgG and IgM antibody specificities for individual polypeptides of Treponema pallidum after therapy for syphilis was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by the Western blot technique. Both IgG and IgM antibodies to as many as 12 treponemal antigens, including a major 47-kdalton molecule, were evident in plasma from patients with untreated primary syphilis. IgM reactivity declined rapidly and uniformly after therapy, whereas IgG persisted despite some diminution in intensity of staining. Faint-to-moderate IgM and strong IgG antibody reactivities to at least 22 treponemal antigens (12-85 kdaltons) were identified in plasma from patients with untreated secondary and early latent syphilis. Again, IgG antibody declined slightly in staining intensity after treatment but continued to show reactivity against all molecules detected initially. IgM antibody reactivity declined more rapidly and was lost entirely against some determinants, including the 14- and 12-kdalton molecules. Immunofluorescence titers of IgG and IgM antibodies to T. pallidum in sera from these patients generally correlated with results of Western blot analysis. Antibody to the 12-, 14-, and 47-kdalton molecules of T. pallidum may have potential diagnostic applications.