Treponema pallidum and HIV are both sexually transmitted agents of infectious diseases with epidemiological similarities. Ulcerous genital diseases such as primary syphilis facilitate transmission of HIV. An increasing number of case reports gives evidence that in HIV-infected patients secondary syphilis runs a more severe course and may present as syphilis maligna and that neurological complications of secondary and tertiary syphilis seem to occur more frequently and at an earlier stage. The clinical evaluation, interpretation of serology and choice of treatment schedules must take these considerations into account.