We describe seven men with a neurologic disease clinically indistinguishable from multiple sclerosis occurring in association with seropositivity for the human immunodeficiency virus, type 1 (HIV-1). Histopathology of the CNS obtained in three patients (2 by brain biopsy, 1 at autopsy) was consistent with MS. The neurologic symptoms preceded the onset of clinically evident immunosuppression in all patients. In three men, HIV-1 seropositivity was demonstrated concomitantly or within 3 months of the onset of their neurologic disease. In the others, features of MS preceded the demonstration of HIV-1 seropositivity by 41 months, 59 months, 11 years, and 18 years, respectively. Despite the superimposition of varying degrees of cellular immunodeficiency associated with HIV-1 infection, six of these men continued to experience relapsing neurologic symptoms.