Background: CIDP is an autoimmune polyneuropathy. Antibodies against the Node of Ranvier have been described, NF155,NF140/186 and contactin-1. Methods: A retrospective review of patients with CIDP who tested positive for antinodal/paranodal antibodies via Western blot were evaluated. We have included 20 sero-negative CIDP patients. All patients met definite or probable EFNS criteria. clinical, electrophysiological data and response to treatment were obtained. Results: Forty-five patients tested positive for the antibodies. Sixteen were positive for NF155,11 for NF140, 5 for CNTN1,11 were double positive for NF155 and NF140, and 3 were triple positive for NF155, NF140 and CNTN. Age of onset was similar in both seronegative (53.9 ± 3.1 yrs.) versus seropositive(52.3 ± 2.4 yrs.).Chronic presentation manifested in 85% of seronegative, 80% of seropositivepatients.Intrestingly,all triple-positive patients presented with a more acute presentation(i.e,<8 wks.)7/20 seronegative (35%),1/16 NF155, 6/11 NF140,1/5 contactin, 2/11 of doublepositive, 3/3 of triple-positive (28%,13/46) responded to IVIg. Conclusions: No major clinical or electrophysiological differences between groups. triple-positive patients showed 100% response to IVIg.These results cast doubt on the specificity of the Western blot as a clinico-electrophysiologic discriminator. Future testing with cellbased assays will likely provide a robust measure that will guide treatment decision.