Thirty-six HIV-1-infected predominantly well-functioning subjects were followed up for one year by repeated neuropsychological, clinical neurological, neuroradiological, and immunological examinations. Changes in cognitive performance related to the severity of HIV-1 infection as well as to neuroradiological or immunological changes were studied. A decline in cognitive speed and flexibility was found in symptomatic subjects (ARC, AIDS). The impairment was especially pronounced in patients with progression of brain atrophy. These findings suggest a brain pathology underlying the cognitive decline in ambulatory outpatients with symptomatic HIV-1 infection. A practice effect was found in asymptomatic subjects (ASX, LAS) and in those with unchanged CT/MRI scans. No systematic relationship was found between cognitive change and immunological change.