Antiganglioside antibodies (AGA) were determined in sera and cerebrospinal fluids (CSF) from 50 systemic lupus erythematosus (SLE) patients, and age-matched normal controls. The SLE patients were subdivided according to the type of clinical manifestation into two groups: neuropsychiatric SLE and active SLE without neuropsychiatric manifestation. The presence of these antibodies showed a significant correlation between IgG AGA in the CSF and IgM AGA in the serum and neuropsychiatric SLE. Fifteen patients had this antibody in the CSF without detectable levels in the serum. No correlation was seen between anticardiolipin antibodies in the serum of CSF and neuropsychiatric SLE. The present work suggests that antibodies against gangliosides may be a marker for neuropsychiatric SLE and that intrathecal antibody production can result in the development of this manifestation.