The calcium-binding protein S100A12 causes inflammation through interaction with the multiligand receptor for advanced glycation end products (RAGE). Blocking of S100A12 showed promising therapeutic effects in mice. We investigated 31 individuals with Kawasaki disease, and recorded an association between expression of S100A12 and activity of Kawasaki disease. Serum concentrations of S100A12 decreased quickly in 28 patients who responded to treatment with gammaglobulin (from 463 microg/L [SD 316] to 184 microg/L [147] within 24 h, p<0.0001). Since the interaction of S100A12 with multiligand receptors has a key role in inflammatory responses, this protein could serve as a novel target for future therapeutic interventions in inflammatory disorders.