High-dose i.v. immunoglobulin (HD-IVIG) has several distinguishing therapeutic characteristics including rapid clearance of pathogenic antibody, non-immunosuppressive and less adverse effects. In 2009, the first multicenter, randomized, placebo-controlled, double-blind trial of HD-IVIG for pemphigus was conducted in Japan. This clinical trial has proved that 400 mg/kg per day for 5 days administration of IVIG is effective as an adjuvant therapy with systemic steroid therapy and/or immunosuppressive agents. Among the several mechanisms to explain the mode of action of IVIG, several lines of evidence have suggested that neonatal Fc receptor for immunoglobulin (Ig)G (FcRn) plays an important role for rapid clearance of pathogenic antibody in pemphigus induced by HD-IVIG. Additionally, the long suppression of IgG production induced by HD-IVIG has been observed in some cases. Taking these characteristics into consideration, HD-IVIG, which leads to decreased pathogenic IgG, is recommended to use in combination with oral corticosteroids or other immunosuppressants, which suppress the production of pathogenic IgG. This review summerizes experimental and clinical evidences for major mechanism of action in HD- IVIG and how to use it.