The "fornix white line" (FWL) is a brain abnormality detected on magnetic resonance imaging (MRI) in some people with human immunodeficiency virus (HIV) infection. This finding has previously been associated with clinical findings of cognitive disturbance, particularly regarding memory. The current study provides preliminary substantiation of the previously reported clinical finding of FWL-associated memory disturbance through formal psychometric evaluation over time. Specifically, despite comparable baseline performances, 8-10 months later subjects without the FWL improved performance on neuropsychological verbal memory testing, while subjects with the FWL declined; the magnitude of this dissociation on follow-up was 1.5 to 2.2 standard deviations. In contrast, general cognitive status, as assessed through performance on the Mini-Mental State Exam, remained comparable between groups and stable over time. Further, the comparable CD4 count and Karnofsky scores at baseline counters the argument that the FWL is simply a marker of HIV disease progression. These preliminary findings suggest the need for future research of the hypotheses raised thereby; particularly salient is the hypothesis that the FWL may serve as an earlier marker indicating anti-CMV treatment before memory impairment is clinically apparent.