Serum from 20 patients with Guillain-Barré syndrome (GBS), 10 healthy controls and 10 patients with recent cytomegalovirus, Epstein-Barr virus, or Campylobacter jejuni/coli infections was injected into rat sciatic nerve. The 20 GBS patients consisted of 2 groups of 10 patients with different electrophysiological and clinical disease patterns. The main aim of the study was to investigate possible differences in humoral (auto)-immunity between these subgroups. We found no statistically significant differences in electrophysiological or histological parameters between nerves injected with sera from the 2 GBS groups. The sera of the GBS groups caused significantly more compound muscle action potential reduction at 3 to 5 days postinjection than the healthy control sera. No significant difference in nerve conduction was found between nerves injected with GBS serum and serum of patients with proven infections without GBS. Histological analysis of the same nerves that were studied electrophysiologically showed no significant differences in demyelination or other histological parameters between patients and controls at 5 days postinjection. Based on the findings in this study that sera of GBS groups with important differences in disease pattern and sera of patients with proven infection but without GBS show similar in vivo effects on rat nerves, we suggest it may be more likely that these effects are caused by aspecific serum factors associated with immune-system activation, especially by precedent infections, than by specific disease-related factors such as anti-myelin antibodies.