Clinical and experimental findings suggest that humoral factors, such as anti-peripheral nerve antibodies and cytokines, may be implicated in the immunopathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin-6 (IL-6) is a multifunctional cytokine that promotes immunoglobulin synthesis by B lymphocytes. Increased IL-6 release is associated with autoantibody production in a number of immune-mediated and neoplastic disorders. To investigate the possible involvement of abnormal IL-6 release in inflammatory polyneuropathies, we assayed IL-6 levels in the cerebrospinal fluid (CSF) and serum of 23 patients with acute GBS and seven with CIDP. We also studied 69 patients with other non-inflammatory neurological diseases (NIND), 25 with other inflammatory neurological diseases (IND), four with brain tumors (BT), and 15 normal donors (serum alone) as controls. We found detectable levels of IL-6 in the CSF of 57% of GBS, 43% of CIDP, 60% of IND, 75% of BT, and 4% of NIND. In GBS patients, no correlation was found between CSF IL-6 values and other laboratory or clinical parameters, such as CSF total protein, CSF albumin, CSF IgG, CSF/serum albumin ratio, functional disability score, and time elapsed from disease onset. Serum IL-6 levels were increased in six of 23 (26%) GBS, in one of 39 (3%) NIND, and in one of seven (14%) IND, but in none of the CIDP or BT patients. There was no correlation between serum and CSF IL-6 values, but cytokine levels in GBS sera correlated with time elapsed from clinical onset.(ABSTRACT TRUNCATED AT 250 WORDS)