The past decade has seen a marked increase in the number of HIV-infected women in the United States. There has been recent concern that HIV disease in general may progress more rapidly in women than men, and some studies, primarily retrospective reviews, have suggested higher rates of neurologic disease among females. The objective of this study was to assess gender differences in HIV-related central and peripheral nervous system disease over time. Participants were enrolled in a longitudinal cohort study at the University of North Carolina and had annual follow-up evaluations. At baseline, 42 HIV-negative females, 52 HIV-positive females, and 52 HIV-positive males were compared for age, education, mode of infection, absolute CD4 cell count, and plasma/cerebrospinal fluid HIV RNA load. Subjects were evaluated by standardized clinical neurologic, neuropsychological, and laboratory examinations every year. The results indicated that both HIV-positive males and HIV-positive females had poorer neurologic functioning than the control group. However, there was no evidence from the parameters measured that the rate of decline differed between HIV-positive males and HIV-positive females.