Guillain-Barré syndrome (GBS) is an inflammatory disorder that may implicate proinflammatory cytokines such as TNF-alpha in its pathogenesis. We determined serum levels of TNF-alpha and the specific antagonists sTNF-Rs p55 and p75 in 24 patients with GBS at days 1, 15 and 30 of hospitalization. Patients were in the progression phase of the disease at day 1, and in the recovery phase at day 30. They were classified as able to walk (stage A), confined to bed (B), or under assisted ventilation (C). All patients underwent plasma exchange within day 1-12. At day 1, TNF-alpha levels were elevated in 15/24 patients, and sTNF-Rs were elevated in 21/23. TNF-alpha levels had not decreased at day 15, and dropped at day 30 (p < 0.04), whereas sTNF-R p55 remained elevated at day 15 and day 30. The TNF-alpha/sTNF-Rs ratio, estimating active TNF-alpha unbound to sTNF-Rs, decreased from day 1 to day 30 (p < 0.05). A positive correlation was found between disease severity and sTNF-R serum levels (p < 0.01). In conclusion, elevated circulating sTNF-Rs assesses activation of the TNF-alpha system in almost all patients with GBS and correlates positively with disease severity. Drop of TNF-alpha contrasting with sustained elevation of sTNF-R p55 during recovery suggests that sTNF-R p55 may be important in the fading of the neural inflammatory effect of TNF-alpha in GBS.