Human natural immunoglobulin (HunIg) preparation for intravenous use has been used in various diseases. The most typical application of this preparation is agammaglobulinemia. Currently, however, this preparation is being used in the therapy of many other disorders. These include thrombocytopenia, Kawasaki disease, systemic vasculitis, several other disorders of autoimmune origin and systemic inflammation such as sepsis. In some diseases, the clinical improvement following use of HunIg has been dramatic, while in others its effect is not striking. Due to rarity of the side effects, the range of application of HunIg has been recently broadened. Such side effects include transmission of several diseases such as hepatitis and retroviral infections. Before it is recommended for use, however, and primarily due to expense, the efficacy of this drug should be carefully evaluated. The mechanism of action of HunIg is not fully understood. However, it has been suggested that its action may involve blockade of Fc-receptor, an anti-cytokine effect, or inhibition of complement activation. In this review, the mechanism of action of HunIgG and its application in human diseases are discussed.