Guillain-Barre syndrome (GBS) is a transient neurological disorder characterized by an inflammatory demyelination of peripheral nerves. Although the pathogenesis of GBS has not been elucidated, there is increasing evidence pointing to an autoimmune etiology. We have studied the reactivity of GBS sera with various phospholipids which are known to be important constituents of myelin, and serve as autoan-tigens in other autoimmune conditions. Sixteen Guillain-Barre syndrome (GBS) sera were studied for the presence of autoantibodies to ssDNA, dsDNA, cardiolipin (CL), phosphatidyl-ethanolamine (PE), phosphatidyl-choline (PC), phosphatidyl-serine (PS), and brain extract. Six of the 16 GBS sera had autoantibodies to one or more of the antigens studied. Three of the sera contained autoantibodies to brain extract (p<0.05), two of the sera had autoantibodies to dsDNA, ssDNA, CL and PE, and one serum had autoantibodies to PC, and PS. As expected a significant proportion of the lupus sera contained autoantibodies to ssDNA and dsDNA, while the frequency of autoantibodies to different phospholipids was significantly high in sera of patients with systemic lupus erythematosus (SLE) and cerebritis. Absorption of GBS sera with cardiolipin, phosphatidyl-choline, or brain extract inhibited the binding of the sera to cardiolipin. Our results demonstrate that some GBS patients produce autoantibodies to various phospholipid and nuclear antigens. However, these autoantibodies are probably produced as a result of the myelin damage rather than cause the demyelination.