Syphilis presented substantial challenges to nineteenth-century medical and psychiatric services. To illustrate the clinical course and diagnostic challenges associated with neurosyphilis in nineteenth-century Ireland. This paper uses original archival material from the Central Criminal Lunatic Asylum, Dublin to present clinical cases and inform a discussion of related issues. Mr A, a 34-year-old banker convicted of "felonious entry", demonstrated many psychiatric and neurological features of neurosyphilis ("general paralysis of the insane"); he soon became "feeble", "paralytic" and "demented", and died within 2 years. The case of Mr B, a 38-year-old game-keeper convicted of "attempting to upset trains", illustrates diagnostic dilemmas associated with neurosyphilis, especially when complicated by evidence of tuberculosis ("scrofulous diathesis"). The clinical and diagnostic challenges presented by syphilis have changed over the past century, but these cases, combined with recent evidence of syphilis outbreaks, highlight ongoing needs for clinical and epidemiological vigilance.