Pediatric research has been limited regarding the neuropsychologic status in systemic lupus erythematosus (SLE) despite frequent involvement of the central nervous system early in the disease process. SLE is a multisystem autoimmune disorder which often presents with significant neuropsychiatric manifestations including objective neurologic findings and severe psychiatric symptoms. Neuropsychological evaluation provides an objective method for delineating changes in higher cortical functions. We studied 21 pediatric patients who met SLE criteria (12 moderate, 9 mild disease activity) and had no history of CNS damage unrelated to lupus. Mean age was 15.8 years; mean SLE duration at the time of the neuropsychological examination was 2.4 years. Comparison of these SLE patients to a contrast group of 11 patients with juvenile rheumatoid arthritis (JRA) revealed decreased complex problem solving ability for the SLE group. Individual, IQ-adjusted neuropsychological profile analysis yielded a significant difference in the number of specific neuropsychologic deficits for the 2 groups, with impairment rates of 43% for SLE and 18% for JRA. Longer duration of lupus was associated with lower cognitive status. Neuron-reactive antibody studies for IgG and IgM were negative. Results suggest that the prevalence of higher cortical impairment may be as great for younger individuals with lupus as has been documented for older populations.