A circulating immune complex-mediated pathogenesis for lesions of secondary syphilis has been postulated. Textbook descriptions of a lymphoplasmacytic histopathologic picture have contradicted a role for circulating immune complexes in lesion pathogenesis. Four patients with early cutaneous lesions of secondary syphilis were studied. All four patients had serum Raji cell and/or Clq binding assay evidence for circulating immune complexes. Three patients showed a neutrophilic vascular reaction on histologic study of early lesions. The patients studied had immunofluorescence microscopic evidence of immunoreactant deposition in dermal blood vessels (4 hours) and/or a neutrophilic vascular reaction (24 hours) after intradermal histamine injection. Dieterle staining of lesional tissue from all patients showed the presence of treponemal organisms in dermal blood vessels. This new preliminary evidence adds some support to a circulating immune complex-mediated pathogenesis of cutaneous lesions in human secondary syphilis.