Autoantibodies against neuronal antigens occur in sera of patients with systemic lupus erythematosus (SLE). These antibodies may have significance in the pathogenesis of neurological complications of SLE. However, the neuronal structures containing the corresponding autoantigens are poorly known. In our study we assayed circulating antibodies against defined neuronal components--neurofilaments--by an enzyme-linked immunosorbent assay (ELISA) using purified neurofilament polypeptides as targets. Circulating neurofilament antibodies (anti-NF) of IgG class were detected in 21% of 28 patients with SLE and in 6% of 17 patients with rheumatoid arthritis and in none of the 14 patients with primary sicca syndrome and 40 blood donors. The presence of anti-NF could also be confirmed by the indirect immunofluorescence technique using frozen sections of rat spinal cord. In one serum, anti-NF cross reacted with vimentin type of intermediate filaments. The antibodies bound both to the 70 kilodalton and the 200 kilodalton polypeptides of neurofilaments as judged by the immunoblotting technique. Two of 6 anti-NF positive patients had neurological complications.