Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein‐1 (MCP‐1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP‐1 but not interleukin (IL) ‐8 or macrophage inflammatory protein‐1α was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP‐1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP‐1, IL‐8, tumor necrosis factor a (TNF‐α), and IL‐1α were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg × 5 days = total 2 g/kg), respectively, compared with respective control values. GG treatment correlated with a rapid decrease in the circulating levels of MCP‐1 (P = 0.001) but not IL‐8 (P = 0.19) or TNF‐α (P = 0.33). In the sensitive Western blotting, MCP‐1 bound to GG. Furthermore, GG inhibited the MCP‐1‐induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP‐1 in KD, and indicate that GG treatment may block MCP‐1 activity, thus alleviating KD vasculitis. J. Leukoc. Biol. 65: 566–572; 1999.