Pooled therapeutic intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases. The lack of a clear understanding of the mode of action of IVIg has been an obstacle to a more rational use and schedule of administration of IVIg and to the improvement of the existing IVIg preparations. Several nonmutually exclusive mechanisms have been proposed to account for the beneficial immunomodulatory effects of IVIg. These include the functional blockade of Fc receptors on phagocytes, inhibition of the deposition of activated complement components on target cells, modulation of the secretion of cytokines and cytokine antagonists, interference with T and B cell proliferation, neutralization of pathological autoantibodies, and long-term selection of immune repertoires.