Human immunodeficiency virus type 1 (HIV-1) p24 antigen, a putative marker of virus load, was assayed in 79 blood and 83 cerebrospinal fluid (CSF) samples from 90 HIV-1–seropositive individuals with or without demetia. Twenty-eight subjects had no evidence of neuropsychological impairment, 17 had mild impairment without objective evidence of dementia, and 45 were demented. HIV-1 p24 antigen was detected more frequently in CSF samples from demented (19/40) than normal (1/26) or mildly impaired (1/17) subjects and in 67% of individuals with significant dementia (MSK stages 2–4). p24 Antigen was detected less frequently in CSF from demented subjects on antiretroviral drugs than untreated demented individuals. Overall, the sensitivity of the antigen capture assay in CSF among demented individuals was 47.5%; the specificity, 95.0%; positive predictive value, 90.4%; negative predictive value, 66.1%; and the efficieny, 72.2%. A direct relationship was also noted between the degree of congnitive impairment and blood p24 antigen detection frequency and antigen concentration. CD4+ blood lymphocyte counts were lower for demented individuals, and HIV-1 p24 antigen was detected more frequently and p24 antigen concentration was higher in blood and CSF from individuals with low CD4+ blood lymphocyte counts. β2-Microglobulin levels were higher in CSF from demented subjects and correlated directly with CSF p24 antigen concentration. However, in contrast to CD4+ blood lymphocyte counts and β2-microglobulin levels, only p24 antigen concentration correlated with dementia severity. Therefore, p24 antigen can be a useful marker for dementia related to HIV-1 infection.