Infection of the peripheral nervous system with Borrelia burgdorferi can present as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF) pleocytosis and intrathecal antibody production against B. burgdorferi, or as an asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA) and normal CSF findings. According to North American studies, it can also present as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations. Our purpose was to investigate the prevalence of B. burgdorferi antibodies in patients presenting with isolated chronic polyneuropathy (PN) in a European region with high incidence of Lyme disease. Sera from 209 PN patients and 247 healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%) healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal spinal fluid white cell count and they did not differ clinically or electrophysiologically from PN patients without antibodies. None of 20 antibody-positive PN patients responded to antimicrobial treatment. The study shows that, in Europe, chronic distal PN without ACA or other Lyme manifestations is very rarely caused by a B. burgdorferi infection.