This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.