A predictive marker for AIDS dementia complex (ADC) in a cohort of neurologically asymptomatic human immunodeficiency virus type 1 (HIV-1)- infected patients with <200 CD4 cells/μL was sought. Patients were assessed neurologically and neuropsychologically at entry. Blood and cerebrospinal fluid (CSF) were taken for assay of β2-microglobulin (β2M), and neopterin and T cell subsets were assessed from blood. Patients were evaluated every 4 months. Of 37 patients recruited, 35 had sufficient follow-up data. Seventeen patients progressed to ADC stage ≤1. In univariate analyses, concentrations of CSF β2M and neopterin and CD4 cell count were each significantly associated with ADC development. In a multivariate analysis, concentrations of CSF β2M remained significant, with levels >5 mg/L carrying ~17 times the risk of ADC. CSF β2M and neopterin levels and CD4 cell count are useful in identifying patients at risk of ADC and as such can be used to target high-risk patients so therapy can be optimized.