We studied the effect of rituximab in allowing a reduction in dose of intravenous immune globulin (IVIg) in six patients with IVIg-dependent, relapsing immune polyneuropathy. Rituximab (375 mg/m(2) intravenously each week for 4 weeks) was administered in a prospective, open-label design to two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), two with multifocal motor neuropathy (MMN), one with neuropathy and anti-myelin-associated glycoprotein (MAG) antibody neuropathy, and one with Sjögren syndrome (SS) ataxic neuropathy. The primary endpoint was a reduced cumulative IVIg dosage by at least 25% at 1 year after rituximab therapy compared to the previous year. Secondary endpoints included an improved summed strength score by at least 5 points on the Medical Research Council scale, an increased sensory score by at least 4 points, or an improved Rankin disability score by at least 1 grade. Total IVIg dosage decreased by greater than 25% in one patient with SS neuropathy and one with MMN; the dosage was unchanged in one with CIDP, slightly reduced in the patient with anti-MAG neuropathy, and increased in one with CIDP and another with MMN. There was no improvement in secondary endpoints. No adverse events occurred. In this small prospective study, rituximab did not reduce IVIg requirements in the majority of patients with IVIg-dependent, immune-mediated polyneuropathies.