The efficacy of plasma exchange implicates myelinotoxic humoral factors in the pathogenesis of Guillain-Barré syndrome. Candidate factors include autoantibodies to peripheral nerve myelin, which are not unique to Guillain-Barré syndrome; and cytokines such as tumour necrosis factor-alpha (TNF-alpha) which are T cell/macrophage products. Plasma cytokine concentrations were determined in 26 patients with Guillain-Barré syndrome undergoing plasma exchange, 25 with other acute neurological diseases, and 40 healthy controls. Raised TNF-alpha concentrations (> 25 pg/ml) were found in seven of 26 patients with Guillain-Barré syndrome v none of 23 disease controls (p = 0.001). The peak grade of clinical deficit correlated with TNF-alpha concentrations (r = 0.6, p < 0.01). There was no significant difference between interleukin-1 beta or interferon-gamma concentrations in patients and disease controls. The data suggest that TNF-alpha may be a critical factor in the pathogenesis of Guillain-Barré syndrome.