We evaluated the concentration of antineuronal antibodies in paired cerebrospinal fluid (CSF) and serum samples from 19 patients with central and peripheral paraneoplastic neurological syndromes (PNS), using an enzyme linked immunosorbent assay (ELISA) employing recombinant antineuronal antigens (HuD, Yo, Ri, CV2/CRMP5, amphiphysin, PNMA2/Ma2). The specific antibody index (AI) [Qspec/QIgG] was calculated to estimate specific intrathecal antibody synthesis. An AI>1.3 was considered as evidence of intrathecal specific antibody synthesis. 14 (88%) of 16 patients with exclusive or predominant paraneoplastic involvement of the central nervous system (CNS) showed an AI>1.3, indicating a specific intrathecal antibody synthesis, while all three patients with isolated involvement of the peripheral nervous system showed an AI<0.8. All together, in 17 of 19 patients (89%) we found a significant association (p<0.05) between central or peripheral neurological manifestations on the one hand and presence or absence of specific intrathecal synthesis respectively on the other hand. These data support the hypothesis that autoimmunity is involved in the pathogenesis of PNS.