Using a solid-phase radioimmunoassay technique, mean serum IgE concentrations were found to be raised in patients with early syphilis. Antitreponemal specificity of the IgE response was investigated by the fluorescent treponemal antibody absorption test using a fluorescein-isothiocyanate-labelled antiserum against the Fc-fragment of human IgE. Validity of this test procedure was assessed by blocking experiments. The results provide evidence of the antitreponemal specificity of the IgE response in syphilis and indicate a possible role for antitreponemal IgE in the pathogenesis of the Jarisch-Herxheimer reaction and in the immune-complex origin of some of the lesions of secondary syphilis.