Within the past 18 months, we have seen four cases of neurosyphilis at our institution (two of meningovascular syphilis, one of acute syphilitic meningitis, and one of asymptomatic neurosyphilis) in young homosexual men with serologic evidence of exposure to human immunodeficiency virus (HIV). Two of the four patients had neurosyphilis despite previous adequate therapy for early syphilis with benzathine penicillin. Meningovascular syphilis developed in one patient within four months after a primary infection, in a manner consistent with an accelerated course of syphilitic infection. These findings suggest the possibility that HIV infection may alter the natural course of syphilis because of the profound defects in cell-mediated immunity it causes. The possible potentiating effects of HIV on Treponema pallidum infection suggest the need for lumbar puncture in the evaluation of HIV-seropositive patients with syphilis, as well as modifications of the currently recommended treatment regimens for primary, secondary, and latent syphilis and neurosyphilis in this patient population. Neurosyphilis should probably be added to the growing list of infectious complications of the acquired immunodeficiency syndrome (AIDS) and may be the first such complication to appear.