Because Kawasaki disease is a disorder characterized by lymphocyte activation and immune complex destruction of endothelial cells, we examined the effect of administration of high doses of intravenously administered immune globulin (IVIG) on a lymphocyte population with affinity for endothelial cells: the natural killer cells. We found that administration of high doses of IVIG resulted in a significant increase in the activity of natural killer cells and in the numbers of circulating CD16+ cells. Furthermore, a study of patients treated with IVIG for seizure disorders suggests that this effect of IVIG on circulating NK cells is not unique to patients with Kawasaki disease. The beneficial effect of IVIG in the treatment of Kawasaki disease may be due to the ability of IVIG to inhibit interaction between natural killer cells and endothelial cells.