The beneficial effect of intravenous immunoglobulin (IVIg) therapy in patients with autoimmune diseases is at least partially dependent on the content in IVIg of antibodies capable of interacting with variable regions (idiotypes) of autoantibodies. In the present study, we have evaluated the antibody activity to a panel of self and environmental antigens of IVIg preparations and their dimer-enriched fractions. Dimers were either obtained by affinity chromatography of IVIg on Sepharose-bound F(ab')2 fragments of IVIg or by size exclusion gel filtration chromatography of IVIg. Enrichment of IVIg in dimers was found to be associated with an increase in the antibody activity against self-antigens as compared with unchromatographed IVIg. Our findings extend previous observations on enhanced autoantibody content of the affinity chromatography-separated 'connected' fraction of IVIg and suggest that therapeutic preparations of IVIg enriched in dimers may be obtained by size exclusion chromatography. Separation by size increases the feasibility of industrial-scale preparation of IVIg with high dimer content that are endowed with high potential immunomodulatory activity in vivo.