Neutrophil-derived S100A12 is strongly upregulated during the acute stage of Kawasaki disease and decreases significantly in response to intravenous immune globulin (IVIG) treatment, whereas in nonresponders, serum concentrations increases after initial treatment. Decreased S100A12 expression in neutrophils was detected initially in nonresponders but increased significantly after IVIG treatment, suggesting delayed inflammatory response of neutrophils in nonresponders. Furthermore, in vitro S100A12 secretion increased with tumor necrosis factor-alpha (TNF-alpha) stimulation, whereas intracellular levels were lower in neutrophils with the higher TNF-alpha dose, suggesting intracellular depletion. S100A12 expression in neutrophils appears to reflect responsiveness to IVIG treatment and is possibly involved in the pathophysiology of acute vasculitis.