Kawasaki disease (KD) is an acute vasculitis of unknown etiology. Immunoregulatory abnormalities have been thought to contribute to its pathogenesis. Although treatment with intravenous immunoglobulin (IVIG) effectively prevents significant cardiac morbidity, the mechanism by which IVIG produces an effect in KD has yet to be fully elucidated.To investigate the effects of IVIG on the immune system of patients with KD.Eleven patients with KD (mean [SD] age, 2.2 [1.5] years) were enrolled in this prospective study and treated with high-dose IVIG therapy (2 g/kg in 1 or 2 infusions) during the acute phase of the disease. We examined immunological changes, with special reference to Ig levels and 2 previously unassessed cytokines: B cell-activating factor belonging to the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL).Clinical symptoms disappeared quickly in all cases, with no coronary artery abnormalities. IgA and IgM levels responded more rapidly than previously reported and reached a peak between the 3rd and 10th day after the start of IVIG treatment. The mean (SD) BAFF level was high before IVIG treatment (3234 [1904] pg/mL) and decreased significantly (1085 [257] pg/mL) after IVIG treatment, whereas the mean (SD) APRIL level before IVIG treatment (18.0 [10.0] ng/mL) rose significantly (120.6 [41.2] ng/mL). A significant inverse correlation between BAFF and APRIL was observed in patients with KD.These results suggest that IVIG may affect the pathogenesis of KD through alteration of BAFF/APRIL.