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Background and Objectives: Neurocognitive impairment is common in human immunodeficiency virus (HIV)-infected subjects. The relationship of sexually transmitted diseases to neurocognitive changes is unknown. Goal: To establish whether HIV-infected patients with a history of syphilis or gonorrhea have a higher rate of neurocognitive dysfunction. Study Design: Neurocognitive function was measured by a battery of quantitative tests in a 453-person HIV-infected cohort and a 219-person HIV-seronegative control group. Neurocognitive function was then correlated with histories of either syphilis or gonorrhea to assess for possible relationships between these sexually transmitted diseases and neurologic impairment. Results: Human immunodeficiency virus-infected subjects with a history of either syphilis or gonorrhea tended to perform worse on neurocognitive testing than their counterparts. This difference could not be explained by educational attainment, age, race or CD4 cell count, and was not noted in the HIV-uninfected control subjects. Conclusions: Sexually transmitted diseases in HIV-infected subjects are correlated with neurocognitive impairment through an unidentified mechanism.