Five patients infected with the human immunodeficiency virus (HIV) with unusual manifestations of syphilis are reported. The high prevalence of HIV seropositivity among our patients with syphilis, the rapid progression to tertiary disease, the increased severity of the clinical manifestations, inappropriate antibody responses to infection, relapse without reexposure despite "adequate" treatment, and lack of response to penicillin therapy have been observed in these and in other patients. Data are presented to explain these unusual observations.