Intravenous immunoglobulin therapy is useful against various immune system disorders and viral infections. It is generally safe, and serious adverse reactions are uncommon. We report a rare case of acute encephalopathy following intravenous immunoglobulin therapy for human herpes virus 6 infection in a child. MR imaging findings suggest that the dominant causative mechanism of acute encephalopathy is cytotoxic edema, and the findings indicate 2 primary mechanisms. Reversibility of the restriction of water diffusion (low apparent diffusion coefficient value) on diffusion-weighted MR imaging suggests intramyelinic edema in the myelin sheath, and an increase of glutamate and glutamine complex peak on MR spectroscopy suggests excitotoxic injury to the neurons and astrocytes.