At its inception, morphological imaging, like magnetic resonance imaging (MRI), is often not useful in neuropsychiatric systemic lupus erythematosus (NPSLE), although the disease clinically shows cerebral symptoms. Functional imaging, like positron emission tomography (PET), may be a method that offers some advantages. We report a 53-year-old white man with decreased memory and visual disturbances who met four of the American Rheumatism Association (ARA) criteria for the classification of SLE. He was investigated before and after 3 months of therapy using PET and F-18-fluoro-2-deoxy-D-glucose (FDG). Treatment consisted of prednisone (25 mg/day, tapered to 10 mg/day) and cyclophosphamide (daily 100 mg for 3 weeks followed by a drug-free interval of 1 week). For the control group, 15 clinically and neurologically healthy volunteers (5 male, 10 female, aged 48 +/- 7 years) were investigated. All study participants additionally had a cranial MRI. In both controls and the SLE patient, cranial MRI was negative. However, the patient showed a significant hypometabolism in the region parieto-occipital on both sides and the parietal region on the right side before treatment. After treatment metabolism in these regions was within normal limits. Hence, FDG-PET could help to verify brain-onset of SLE earlier and may be a powerful tool for controlling SLE treatment.