No causative or curative therapy exists for the polyneuropathy associated with antibodies to myelin-associated glycoprotein (anti-MAG). Rituximab is a mouse-human chimeric antibody that specifically eliminates B-cells and B-cell precursors. Preliminary results suggest a beneficial effect on antibody-dependent autoimmune diseases. Nine patients with an anti-MAG-associated IgM polyneuropathy received rituximab once weekly for 4 weeks. In all patients, the number of B-cells in the peripheral blood declined below levels of detection, and the IgM levels decreased between 35% and 82% (median, 58%). In eight patients, lowering of the anti-MAG antibody titers of more than 52% was observed. Clinical status improved in six patients, remained stable in two, and worsened in one. The motor nerve conduction velocity improved by at least 10% in one ulnar nerve in seven patients and worsened in two. Rituximab was well tolerated and is a promising new drug in the treatment of patients with anti-MAG-associated polyneuropathy.