Immunoglobulin preparations enriched with IgM and IgA are used in the therapy of severe bacterial infections and for the treatment of acute graft-versus-host disease, but not as yet, in the treatment of autoimmune diseases. We investigated the potential of an IgM- and IgA-enriched immunoglobulin preparation to neutralize activity autoantibodies from patients with autoimmune diseases. We demonstrate that Pentaglobin(R) was at least as effective as intravenous immunoglobulin (Sandoglobulin(R)) in inhibiting autoantibody activity. Each of the immunoglobulin isotypes present in Pentaglobin(R) may be responsible for the inhibitory effect. Pentaglobin(R) immobilized on an affinity matrix retained the disease associated autoantibodies and interacted with F(ab')2 fragments of IgG autoantibodies. Suppression of autoantibody activity is dependent, at least in part, on idiotypic interactions. The present findings provide a rationale for considering these preparations for the immunomodulation of autoimmune disease.