Characterization of Guillain-Barré syndrome (GBS) subtypes has become increasingly complicated with the recognition of paranodal dysfunction and reversible conduction failure (RCF) in acute motor axonal neuropathy. We describe 2 cases of seronegative acute motor axonal neuropathy with RCF with a rapid onset of severe quadriplegia. Treatment with plasma exchange was associated with rapid clinical and electrophysiological response on serial examinations. Increased recognition of RCF may lead to improved characterization of GBS subtypes and may play a role in determining future treatment options in GBS.