BACKGROUND Acute Guillain-Barré syndrome (GBS) is a disease where cell-mediated and humoural immune reactions play a key role. Breakdown of the blood-nerve barrier, inflammation of the nerve roots and conduction block are leading symptoms. As it is likely that pathological humoural or cellular factors are concentrated in the subarachnoid space and since factors in the cerebrospinal fluid (CSF) of GBS patients were shown to block sodium channels, a direct therapeutic intervention in the intrathecal compartment seemed worthwhile. METHODS For this purpose, we developed a technique to purify CSF from pathological factors. Filtration was achieved by withdrawal of CSF (through a lumbally inserted 18 G catheter) and reinfusion via specially developed filters. RESULTS Twenty severely affected GBS patients were treated with 4 to 38 CSF filtrations. This eliminated cells (> 99%) and reduced the protein content. Clinical improvement was achieved probably by improvement of nerve conduction following a reduction of sodium channel blocking factors. The median time to one grade improvement was 19 days, to reach grade 2 (independent walking) was 42 days. Ventilated patients were weaned from the ventilator after 16 days (median). Patients for which CSF filtration was the first kind of treatment improved faster than patients that had not responded to other treatments, such as plasma exchange or intravenous immunoglobulins. CONCLUSIONS Severe side effects were not observed, except sometimes transient headache during the withdrawal phase. This therapy seams to shorten treatment time (in comparison to times reported in studies with and without GBS-specific treatment by plasma exchange or immunoglobulins) and to reduce the degree of remaining neurological deficits. An open randomized controlled study is currently being conducted to compare CSF filtration with plasma exchange.