Immunoglobulin class-specific Clq-solid-phase assays were used to detect circulating immune complexes in the sera of infants with congenital syphilis. Elevated levels of IgM complexes were present in the sera of all infants with overt disease and in two of 14 asymptomatic infants considered to be "at risk." The sera of infants born to normal, serofast, and biologic false-positive mothers did not contain immune complexes. Immunoblotting techniques revealed that complexes isolated from the sera of the infected infants contained endogenous host antigens, as well as a limited number of treponemal polypeptides. Consistent with earlier findings examining purified immune complexes from adults with secondary syphilis and from infected animals, an 83-kilodalton Treponema pallidum antigen was present in all of the isolated complexes from infants with congenital syphilis. Our findings emphasize the fact that current serological and clinical measures of infection are inadequate and that certain "at risk" infants should be treated despite normal cerebrospinal findings and the absence of clinical manifestations.