The aim of the present study was to investigate the role of antinuclear and antiphospholipid antibodies in the pathogenesis of systemic lupus erythematosus (SLE) with demyelinating syndrome and several forms of multiple sclerosis (MS). Paired samples of serum and cerebrospinal fluid (CSF) were investigated using laser nephalometric and enzyme linked immunosorbant assay (ELISA) methods, and the parameters of intrathecal synthesis were calculated. Elevation of the concentrations of antiribosomal P protein antibodies in the CSF and serum, and intrathecal synthesis anticardiolipin (aCL) antibodies were characteristic in all patient groups. The immunoserological changes were more pronounced in the SLE patients. A similar pathogenetic role of antiphospholipid antibodies in central nervous system (CNS) damage in SLE patients with demyelinating syndrome and of MS patients can be assumed.