Guillain-Barré Syndrome (GBS) is an acute post infectious or disimmune illness that affects nerve roots and peripheral nerves. Multicenter studies have clearly shown that plasma exchange (PE) provides valuable amelioration of GBS. It was recently suggested that plasma perfusion (PP) on phenylalanine columns displays the same therapeutic effects of PE in neuroimmunologic disorders, without the infectious risks linked with plasma replacement. In this study, the authors compared the efficacy of PE versus that of PP in two groups of patients suffering from GBS by investigating the clinical outcomes and the electrophysiologic and cerebrospinal fluid findings. Of 22 patients suffering from GBS, 16 underwent seven sessions of PE in a mean time of 15 days (Group A). Six patients, showing the same clinical pattern, underwent three sessions of PP in a mean time of 10 days (Group B). Data reported in Group A show that PE: 1) stops the progressive worsening of the disease, 2) prevents the development of acute respiratory failure, 3) allows an early and significant clinical improvement with change in disability grade, and 4) improves motor conduction velocities and motor action potentials when recorded 45 days after the end of treatment. Data in Group B show that PP allows a slower and later improvement in disability grade, and electrophysiologic data recorded at the end of treatment was worse after 45 days. Finally, it may be concluded that PE has beneficial effects on GBS in terms of time of recovery, complication rate, and relapses. Plasma perfusion did not show the same results.